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A one-year prospective study of infectious etiology in patients hospitalized with acute exacerbations of COPD and concomitant pneumonia
Abstract
This study assessed the infectious etiology of patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with concomitant pneumonia.
Patients admitted to medical wards in an acute hospital were recruited prospectively from May 1, 2004 to April 30, 2005. Sputum culture, blood culture, paired serology, and nasopharyngeal aspirates (NPA) viral culture and polymerase chain reaction (PCR) studies were performed. Spirometry was assessed in stable phase at 2-3 months post-hospital discharge.
Seventy eight subjects were admitted for AECOPD with concomitant pneumonia. The mean (SD) age was 77.1 (7.5) years, with FEV(1) of 41.5 (20.8)% predicted normal. Overall, an infectious etiology could be established in 48.7% of the subjects. Among the 71 subjects with sputum collected, 40.8% had positive bacterial culture. The commonest bacteria identified were Streptococcus pneumoniae (8[11.3%]), Pseudomonas aeruginosa (7[9.9%]) and Haemophilus influenzae (7[9.9%]). Among the 66 subjects with NPA collected, 9.0 and 12.2% had positive viral culture and PCR results, respectively. The commonest viruses identified by NPA PCR were influenza A (4[6.1%] subjects) and rhinovirus (2[3.0%]). Paired serology was positive in 4.4%. Patients on high dose inhaled corticosteroid (ICS) (>1000 mcg beclomethasone-equivalent/day) had a higher rate of positive sputum bacterial culture than those on low-medium dose of ICS (50.0% vs 18.2%, p=0.02).
An infectious etiology could be established in about half of patients hospitalized with AECOPD and concomitant pneumonia. The majority of identifiable causes were bacterial. Patients on high dose ICS might have impaired airway defense as reflected by the higher rate of positive sputum culture.
... Повышение интереса к проблеме пневмонии у больных ХОБЛ в последнее время связано с появ лением относительно новых данных о поддерживаю щей терапии ингаляционными глюкокортикостеро идами (иГКС) как факторе риска развития ВП [31,32]. Данные о микробном спектре возбудителей пнев монии у больных ХОБЛ также изучены недостаточ но [26,27,33]. Диагностика ВП у больных с обостре нием ХОБЛ, а особенно при наличии сложного коморбидного фона, представляет значительные трудности. ...
... Возбудители ВП у больных ХОБЛ в настоящем ис следовании идентифицированы в почти 1 /2 случа ев (48 %). Основными этиологическими агентами ВП были S. pneumoniae (21,7 %), K. pneumoniae (8,6 %), S. aureus (8,6 %) и Р. aeruginosa (4,3 %), что согласует ся с данными других исследований [17,30,33]. В на шем недавнем исследовании бактериальные возбу дители были идентифицированы у 53 % пациентов с ВП, явившейся причиной ОДН при ХОБЛ [30]. ...
... (12 %) и др. F.W.S.Ko et al. недавно провели исследование, в котором изучили этиологию ВП у 78 больных с обострением ХОБЛ при помощи посева мокроты, вирусологической культуры аспирата носоглотки, полимеразной цепной реакции (ПЦР) аспирата но соглотки и серологического анализа парных сыворо ток [33]. Суммарная частота идентификации микро организмов всеми использованными методами составила 48,7 %. ...
... P = 0.02). [60] Among patients with CAP and COPD, S. pneumoniae remains the most common cause, but H. influenzae, Moraxella catarrhalis, and P. aeruginosa are also often isolated in CAP. [10,11,61] Infection with P. aeruginosa has been shown to be associated with an older patient population and regular oral corticosteroid therapy. ...
... [10,11,61] Infection with P. aeruginosa has been shown to be associated with an older patient population and regular oral corticosteroid therapy. [60] Due to chronic bacterial colonization, the etiological diagnosis of pneumonia can be challenging for sputum culture diagnosis, as in 4-15% of patients with COPD, P. aeruginosa was isolated from sputum in patients without pneumonia. [62] Therefore, the isolated rates of P. aeruginosa in sputum may be overstated. ...
... In patients with AECOPD and concomitant pneumonia, bacterial pathogens have been reported to be more commonly isolated etiological agents when compared with viruses, which has been supported by a prospective study that reported that the overlap between viral and bacterial etiologies was low. [60] Mohan et al. [63] showed that the prevalence of viral respiratory infections among patients with AECOPD was up to 34.1%, and included infection by picornavirus (17.3%) and influenza virus (7.4%). Picornavirus was found to be the most common virus associated with CAD in Western countries; influenza virus was found to be the most common virus associated with CAD in Asia. ...
Objective:
Worldwide, community-acquired pneumonia (CAP) is a common infection that occurs in older adults, who may have pulmonary comorbidities, including chronic obstructive pulmonary disease (COPD). Although there have been clinical studies on the coexistence of CAP with COPD, there remain some controversial findings. This review presents the current status of COPD in CAP patients, including the disease burden, clinical characteristics, risk factors, microbial etiology, and antibiotic treatment.
Data sources:
A literature review included full peer-reviewed publications up to January 2018 derived from the PubMed database, using the keywords "community-acquired pneumonia" and "chronic obstructive pulmonary disease".
Study selection:
Papers in English were reviewed, with no restriction on study design.
Results:
COPD patients who are treated with inhaled corticosteroids are at an increased risk of CAP and have a worse prognosis, but data regarding the increased mortality remains unclear. Although Streptococcus pneumoniae is still regarded as the most common bacteria isolated from patients with CAP and COPD, Pseudomonas aeruginosa is also important, and physicians should pay close attention to the occurrence of antimicrobial resistance, particularly in these two organisms.
Conclusions:
COPD is a common and important predisposing comorbidity in patients who develop CAP. COPD often aggravates the clinical symptoms of patients with CAP, complicating treatment, but generally does not appear to affect prognosis.
... On the other hand, the role of respiratory viruses in CP-COPD has not been well investigated. Until recently, there have been only a few reports on the role of respiratory viruses in CP-COPD patients [Mallia and Johnston, 2007;Ko et al., 2008;Molinos et al., 2009;Vanspauwen et al., 2012]. Moreover, these previous studies have several limitations. ...
... Moreover, these previous studies have several limitations. Some were focused on a specific virus such as influenza virus [Mallia and Johnston, 2007] or an RT-PCR test was performed in only small portion of the studies patients [Ko et al., 2008;Molinos et al., 2009]. Furthermore, to the best our knowledge, none of the prior studies compared the viral etiologies and their clinical outcomes between AE-COPD and CP-COPD. ...
... Here, we found that influenza virus (14.1%) was the most commonly identified virus in the AE-COPD group, followed by rhinovirus (10.4%). The Hong Kong group also showed that influenza virus was most commonly identified in AE-COPD patients [Ko et al., 2008]. However, these findings should be interpreted with caution as both studies included AE-COPD patients who were admitted to general hospitals.. Therefore, a bias might have been introduced if less severely affected patients did not come to our tertiary care hospital. ...
Aim:
Respiratory viruses are well-known causes of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) and also important pathogens for concomitant pneumonia in COPD (CP-COPD). However, the differences in a viral infection pattern and clinical impacts of respiratory viruses between the two groups have not been well investigated.
Methods:
The clinical and microbiological data from COPD patients admitted with AE-COPD (n = 281) or CP-COPD (n = 284) between January 2010 to December 2012 were reviewed. After excluding 88 patients (40 with AE-COPD and 48 with CP-COPD) who did not undergo a multiplex RT-PCR test for respiratory viruses, the demographic characteristics, identified viruses, and clinical outcomes of the AE-COPD and CP-COPD groups were compared.
Results:
Respiratory viruses were identified in 41.9% of AE-COPD group and 33.5% of the CP-COPD groups. The most common virus was influenza virus in the AE-COPD group (33.7%) vs. human coronavirus (24.1%) in the CP-COPD group. Influenza virus was significantly more common in the AE-ACOPD group than in the CP-COPD group (P < 0.01). In-hospital mortality of AE-COPD and CP-COPD were 1.2% and 12.3%, respectively (P < 0.01). Among CP-COPD patients, in-hospital mortality of patients with only viral infection group, only bacterial infection group, and viral-bacterial co-infection were 2.6%, 25.8%, and 17.5%, respectively (P = 0.01).
Conclusions:
Respiratory viruses were commonly identified in both AE-COPD and CP-COPD, influenza virus and human coronavirus were the most common viruses identified in AE-COPD and CP-COPD patients, respectively. The mortality rates of only viral infection group was significantly lower than only bacterial infection or viral-bacterial co-infection group in CP-COPD patients. This article is protected by copyright. All rights reserved.
... Adults seem to show a slightly lower prevalence of viral infection during exacerbations. Finally, 22 to 64% of patients with COPD exacerbations have virus identified by PCR versus 12 to 19% of nonexacerbating subjects2223242526. Across all of these studies, RV makes up approximately 50% of the viruses isolated (Table 2). ...
... Finally, oxidative stress resulting either from inhaled oxidants or inflammatory cells plays a significant role. As mentioned above, about one half of COPD exacerbations are associated with viral infections, the majority of which are due to RV2223242526 . COPD exacerbations may also be associated with the isolation of the new bacterial strain [110]. ...
Over the past two decades, increasing evidence has shown that, in patients with chronic airways disease, viral infection is the most common cause of exacerbation. This review will examine the evidence for viral-induced exacerbations of asthma and chronic obstructive lung disease and the potential mechanisms by which viruses cause exacerbations. Attention will be focused on rhinovirus, the most common cause of respiratory exacerbations. Exacerbations due to rhinovirus, which infects relatively few cells in the airway and does not cause the cytotoxicity of other viruses such as influenza or respiratory syncytial virus, are particularly poorly understood. While the innate immune response likely plays a role in rhinovirus-induced exacerbations, its precise role, either adaptive or maladaptive, is debated. Because current treatment strategies are only partially effective, further research examining the cellular and molecular mechanisms underlying viral-induced exacerbations of chronic airways diseases is warranted.
... Note: Total viral and human rhinovirus exacerbation rates in seven studies of exacerbations of chronic obstructive pulmonary disorder.45–50,54 ...
... Several studies looking at causes of exacerbations in COPD have shown that viruses account for up to 60% of exacerbations, and that HRV is numerically the most important virus type.30,45–50
Figure 3 depicts the total viral and HRV exacerbation rate in seven exacerbation studies. Other viruses associated with acute exacerbations of COPD are coronavirus, influenza A and B, parainfluenza, adenovirus, and respiratory syncytial virus.45,51–55 ...
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Current therapies confer partial benefits either by incompletely improving airflow limitation or by reducing acute exacerbations, hence new therapies are desirable. In the absence of robust early predictors of clinical efficacy, the potential success of novel therapeutic agents in COPD will not entirely be known until the drugs enter relatively large and costly clinical trials. New predictive models in humans, and new study designs are being sought to allow for confirmation of pharmacodynamic and potentially clinically meaningful effects in early development. This review focuses on human challenge models with lipopolysaccharide endotoxin, ozone, and rhinovirus, in the early clinical development phases of novel therapeutic agents for the treatment and reduction of exacerbations in COPD.
... In our study, there was no significant difference in the presence of any infection among male and female patients (p > 0.05), which was similar to that reported by Voiriot et al. [15]. Ko et al. reported that concomitant pneumonia and COPD were the 5th leading causes of death [23]. Among the 68 patients with COPD, 23 patients had bacterial infection alone, 25 patients had viral infection alone and 14 patients had bacterial-viral co-infection. ...
Introduction:
The use of mechanical ventilators in the intensive care unit (ICU) is often associated with higher risk of respiratory tract infections, including ventilator-associated pneumonia (VAP). Concomitant bacterial-viral infection was reported to worsen patient's clinical condition. This study evaluated the rate of concomitant bacterial-viral infections in patients with VAP and analyzed their clinical outcomes.
Methodology:
In this retrospective observational study 107 patients diagnosed with VAP and admitted in ICU with mechanical ventilator support between April 2018 and May 2019 in the Department of Respiratory Medicine, Dachang Hospital, Shanghai, China were included. 27 most commonly involved lower respiratory tract infection (LRTI) pathogens (bacteria and virus) and seven genetic markers of antibiotic resistance were detected and analyzed using Biofire® FilmArray® Pneumonia Panel plus (bioMérieux SA, Paris, France).
Results:
Of the 107 patients, 45 (42.1%) patients had bacterial infection alone (bacterial group), 26 (24.3%) had virus infection alone (viral group) and 24 (22.4%) patients had concomitant bacterial-viral infection (mixed group). Sixty-nine (64.5%) and 50 (46.7%) patient samples were positive for bacterial (bacterial and mixed groups) and viral (viral and mixed groups) detection, respectively. Streptococcus pneumonia (11.2%) and Influenza A (17, 15.9%), were the predominantly identified bacterial and viral species. The blaCTX-M (21.5%) was the predominant resistance gene detected. Twenty-four (22.4%) patients were positive for concomitant bacterial-viral infection; Staphylococcus aureus and Influenza A were the most common bacterial-viral combination identified.
Conclusions:
Concomitant bacterial-viral infection was higher compared to previously published studies and the increased duration of mechanical ventilation was associated with increased disease severity.
... В исследовании F.W.S.Ko et al. у больных ХОБЛ с ВП, постоянно получавших высокие дозы иГКС (> 1 000 мкг в перерасчете на бекламетазон), частота выделения микроорганизмов из мокроты была вы ше, чем у пациентов, принимавших низкие и сред ние дозы иГКС (50 % vs 18,2 %) [60]. Кроме того, у больных, принимавших иГКС до госпитализации, чаще выявлялась вирусная природа респираторной инфекции (с помощью всех использованных мето дов) по сравнению с пациентами, не принимавшими иГКС (26,3 % vs 5,8 %). ...
... However, Pseudomonas aeruginosa (PA) and other gramnegative bacilli are more likely to be observed in older hospitalized patients with COPD and CAP, as well as those who have poorer lung function, are receiving oral corticosteroid treatment and require IMV and an ICU admission, and could significantly predict an increased risk of exacerbation that requires hospitalizations or allcause mortality. [5][6][7][8][9][10][11] Furthermore, previous studies have reported that Acinetobacter spp. is one of the major bacterial isolates in patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) in Asia as well as in Taiwan. Meanwhile, infection with Acinetobacter spp. ...
Purpose:
Little is known about the features and implications of Pseudomonas aeruginosa (PA) and Acinetobacter baumannii complex (ABC) isolates discovered in patients with chronic obstructive pulmonary disease (COPD) and community-acquired pneumonia (CAP) requiring invasive mechanical ventilation and admission to an intensive care unit. Thus, our study aimed to investigate the clinical characteristics and antimicrobial susceptibilities of PA and ABC isolates cultured from endotracheal aspirates (EAs) in such population.
Patients and methods:
In this retrospective, cross-sectional study, clinical data from medical records were reviewed and collected for analysis.
Results:
Of the 262 participants, 17.2% (45/262), 11.5% (30/262), and 27.1% (71/262) had PA, ABC, and any of the two isolates discovered from EA cultures, respectively. Patients with PA isolates were associated with poorer lung function (the Global Initiative for Chronic Obstructive Lung Disease (GOLD) III+IV versus GOLD I+II, odds ratio (OR)=2.39, p= 0.022) and a lower body mass index (per increase of 1 kg/m2, OR= 0.93, p= 0.106) while the former was an independent predictor. Moreover, both subjects with ABC isolates and those with any of these two microorganisms were independently associated with a lower serum albumin level (per increase of 1 g/dL, OR= 0.44, p=0.009 and OR= 0.59, p=0.023, respectively). Participants with PA isolates were more likely to have failed weaning (62.2% versus 44.7%, p= 0.048) and death (28.9% versus 12.4%, p= 0.010) than those without PA isolates. The majority of the PA and ABC isolates were susceptible and resistant to all the tested antimicrobials, respectively, except that tigecycline had a reliable activity against ABC.
Conclusion:
Our findings provide important information to help intensivists make better treatment decisions in critically ill patients with COPD and CAP.
... 86 The utilization of oral corticosteroid therapy for COPD exacerbations is associated with P. aeruginosa infection. 87 Finally, prior antibiotic therapies in patients with frequent exacerbations can result in a change of lung ecology leading to P. aeruginosa infection. 19,21,82 Furthermore, patients with a compromised immune system, such as HIV-infected patients, neutropenic patients, and those on immunosuppressive or immunomodulatory agents, are also prone to P. aeruginosa CAP. ...
In recent decades, there has been a growing interest about the role of gram negative bacteria in community-acquired pneumonia (CAP), especially Pseudomonas aeruginosa, Enterobacteriaceae, and Acinetobacter baumannii. The prevalence of these pathogens differs largely according to the local ecology and the geographical location. Identifying gram negative bacteria, and in particular resistant gram negative bacteria, is of paramount importance in patients with CAP because these pathogens are associated with higher clinical severity and unfavorable outcomes. The use of individualized risk factors to predict each pathogen is a helpful strategy that needs to be locally validated. However, it should be taken into account that most of the risk factors identified in the literature are heterogeneously defined or lack consistency. New diagnostic techniques, such as molecular testing, are promising methods for early detection of these gram negative pathogens. The increasing mechanisms of resistance to antibiotics of these pathogens have limited our therapeutic approach. This narrative review focuses on the epidemiology, risk factors, diagnosis, and therapeutic options for the most relevant gram negative bacteria that cause CAP.
... Other published studies have also reported that S. pneumonia was the most commonly isolated bacterium implicated in CAP (16,17). Furthermore, there is growing support for the opinion that bacteria can also play an important role in infectious exacerbations of asthma and COLD (18)(19). ...
... However, as HRVs are commonly detected from subjects with mild respiratory symptoms, and even from asymptomatic individuals, the role of rhinovirus detected in the upper airways as a causative agent of viral pneumonia is still questioned [72,75]. To further complicate the scenario, HRV is often found together with S. pneumoniae or other pathogenic bacteria in patients with pneumonia [47]. Viral-bacterial pneumonia has a poorer response to treatment than pneumonia caused by a single agent. ...
There is an association with acute viral infection of the respiratory tract and exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Although these exacerbations are associated with several types of viruses, human rhinoviruses (HRVs) are associated with the vast majority of disease exacerbations. Due to the lack of an animal species that is naturally permissive for HRVs to use as a facile model system, and the limitations associated with animal models of asthma and COPD, studies of controlled experimental infection of humans with HRVs have been used and conducted safely for decades. This review discusses how these experimental infection studies with HRVs have provided a means of understanding the pathophysiology underlying virus-induced exacerbations of asthma and COPD with the goal of developing agents for their prevention and treatment.
... Viral pattern was similar to the local influenza activity [23]. Similarly, influenza virus was shown to be predominant viral pathogen in CAP in Spain [5,16], in patients with acute exacerbations of COPD and concomitant pneumonia in Hongkong [24], while in New Zealand, rhinovirus was the most commonly identified pathogen, followed by influenza virus and RSV [3]. Difference in the prevalence of specific virus infection among studies may relate to diverse geographical, climate, activity of the virus pandemic in the community locally, testing assays applied and the viral pattern studied, etc. ...
Background
Viral pathogens were more commonly reported than previously estimated in community-acquired pneumonia (CAP) patients. However, the real role of virus was still controversial.
Methods
Consecutive adult patients with CAP between April and December, 2009 were prospectively enrolled. A four-fold or greater increase of IgG-titres against respiratory viruses in pair sera was tested by means of hemagglutination inhibition assay or indirect immunofluorescence. Swab samples were tested by cell culture and/or nucleic amplification tests. Viral etiology was considered definitive if at least one of the above tests was positive.
Results
Viral etiology was established in fifty-two (34.9%) of 149 CAP patients, twenty-two (81.5%) of 27 influenza like illness patients, and none of 75 volunteer controls. Forty-seven CAP patients were infected by a single virus (24 influenza A virus, 5 influenza B, 10 parainfluenza virus type 3 [PIV-3], 2 PIV-1, 2 adenovirus, 2 human rhinovirus and 2 coronavirus OC43), five cases by two or three viruses co-infection. Fever ≥ 39°C (66.7%), fatigue (64.6%), and purulent sputum (52.1%) was the most common symptoms in viral pneumonia patients. On multivariate analysis, myalgia was included in the model for pneumonia associated with influenza infection. In the CURB-65 model only influenza infection was found independently associated with severe disease (CURB-65 score ≥ 3) out of variables, including age(years), sex, current smoking status, sick contact with febrile patients, numbers of comorbidity, presence of influenza infection, presence of PIV infection, with P = 0.021, OR 7.86 (95% CI 1.37-45.04).
Conclusion
Respiratory virus was not a bystander, but pathogenic in pneumonia and was a common cause of CAP.
... 4 Fanny et al found that the most frequent pathogens of COPD exacerbation were Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, and Pseudomonas aeruginosa. 5 COPD exacerbation and community-acquired pneumonia usually cause some of the symptoms of respiratorytract infections, such as fever, purulent sputum, an increase in white blood cells, and an increase in C-reactive protein. Additionally, COPD exacerbation often coexists with community-acquired pneumonia, and several studies have found that early-onset COPD exacerbation and community-acquired pneumonia have similar pathogenic spectrums. ...
To study the differences in pathogen distribution and antibiotic susceptibility between patients with COPD exacerbation and patients with community-acquired pneumonia, and develop guidance for antibiotic treatment of those conditions.
We retrospectively analyzed the medical records of 586 COPD-exacerbation patients and 345 community-acquired-pneumonia patients from January 2007 to December 2008, including sputum culture results, antibiotic susceptibilities of the microorganisms, and clinical characteristics.
276 (47%) of the COPD-exacerbation patients, and 183 (53%) of the community-acquired-pneumonia patients had a positive sputum culture. In order, the most common pathogens in the COPD-exacerbation patients were Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Acinetobacter baumannii, and Haemophilus influenzae. The most common pathogens in the community-acquired-pneumonia patients were Streptococcus pneumoniae, H. influenzae, K. pneumoniae, S. aureus, and E. coli.
P. aeruginosa was the most common pathogen in our patients with COPD exacerbation, and S. pneumoniae was the most common in our patients with community-acquired pneumonia. P. aeruginosa is especially common in the patients with serious or extremely serious COPD.
... As 20 subjects could not perform satisfactory spirometry whereas 64 subjects were unable to perform 6-MWT (either too breathless to walk, having arthritis or old cerebrovascular accident that limited their mobility) at the baseline study, we have only included 243 subjects for our analysis. 29.5%(18/61), 6.6%(4/61), 13.1%(8/ 61) died of COPD, pneumonia, and lung cancer respectively. ...
BODE index comprises Body mass index, Obstruction of the airway [FEV(1)], Dyspnoea score [modified Medical Research Council questionnaire] and Exercise capacity [6 min walk test]. This study assessed the role of serial changes in BODE index in predicting mortality and readmissions of COPD patients.
A prospective cohort study involving 243(208 males) COPD patients hospitalized for acute exacerbations of COPD [AECOPD]. BODE index was assessed at 6 weeks(baseline), 6, 12, 18 and 24 months post hospital discharge. Mortality and readmissions in the subsequent 3 years were recorded. All the patients were managed by usual care without additional intervention.
The mean (SD) age and FEV(1)% predicted were 74.2(7.8) yrs and 51.7(21.6)% respectively. Over the 3 years, 25.1% died whereas 76.5% had at least 1 readmission for AECOPD. Baseline BODE index was predictive of both the survival and readmissions to hospital for AECOPD by Cox regression analysis (p < 0.001 for both survival and readmissions). Over 24 months, 71(40.1%), 94(53.1%), 12(6.8%) patients had increased (>1 point), no change, and decreased in BODE (>1 point) index respectively. Serial changes in BODE index at 6 month was marginally associated with mortality, but not at 12-, 18- and 24-month. The 6-, 12- and 24-month BODE indices were predictive of the readmissions for AECOPD when compared to baseline.
Baseline BODE index could predict both survival and readmissions for AECOPD, whereas serial BODE indices were not predictive of survival at 3 years. Single rather than serial measurements of BODE index is sufficient for prediction of survival and readmissions for patients treated with usual care.
... Other published studies have also reported that S. pneumonia was the most commonly isolated bacterium implicated in CAP (16,17). Furthermore, there is growing support for the opinion that bacteria can also play an important role in infectious exacerbations of asthma and COLD (18)(19). ...
There is a deficiency in the data concerning the role of hMPV in lower respiratory tract infections in adults, and until now there has been no data available regarding the prevalence of hMPV in adults in our region. In the present study the association of hMPV with varieties of lower respiratory tract disorders in immunocompetent adult patients, either alone or with bacterial pathogens, has been highlighted.
Eighty-eight patients were included in the study. They included 46 males and 42 females with an age range of 38–65 years. Patients presented with lower respiratory tract infections associated with acute exacerbation of asthma (67%), pneumonia (17%), and acute exacerbation of chronic obstructive lung diseases.
Sputum and nasopharyngeal samples were obtained from the patients and subjected to a full microbiological study. In addition, detection of hMPV was performed by nested reverse transcriptase polymerase chain reaction.
The pathogens isolated were Streptococcus pneumoniae 46.6%, Staphylococci aureus 35.2%, and human metapneumovirus 13.6%. Influenza virus and rhinovirus were each isolated from 4.5% of patients. Human metapneumovirus was associated with S. pneumoniae in 4.5% in studied patients, while in 9.1% it was the only pathogen found in those patients. The commonest clinical condition with significant association with human metapneumovirus was pneumonia.
The clinical and laboratory studies demonstrated an association between lower respiratory tract infections in adults and hMPV either as sole pathogen or in association with Streptococcus pneumoniae. It was a common pathogen in community-acquired pneumonia.
Objectives The clinical implications of blood eosinophil level in patients with chronic obstructive pulmonary disease (COPD) and community-acquired pneumonia (CAP) requiring invasive mechanical ventilation (IMV) and intensive care unit (ICU) admission are still unknown. Thus, this study aimed to compare the features of such patients with and without blood eosinophilia.
Design This was a retrospective case–control study. setting An ICU of a medical centre in central Taiwan. Participants A total of 262 patients with COPD and CAP requiring IMV and ICU admission.
results Of all participants (n=262), 32 (12.2%) had
an eosinophil percentage (EP) >2% and 169 (64.5%)
had an absolute eosinophil count (AEC) >300 cells/μL. Regardless of whether 2% or 300 cells/μL was used
as a cut-off value, the eosinophilia group were slightly older (years) (82.9±5.4 vs 78.1±9.1, p=0.000 and 79.2±8.4 vs 77.6±9.6, p=0.246, respectively), and had
a higher forced expiratory volume in 1 s/forced vital capacity (%) (56.0±8.0 vs 51.3±11.6, p=0.005 and 53.1±11.2 vs 49.5±11.2, p=0.013, respectively), less severe spirometric classification (p=0.008 and p=0.001, respectively), and lower white cell count 109/L (8.8±3.2 vs 11.1±4.9, p=0.009 and 10.3±4.4 vs 11.8±5.3, p=0.017, respectively) than the non-eosinophilia group. The bacteriology of endotracheal aspirates showed that Pseudomonas aeruginosa and other gram-negative bacilli were the most common organisms in all study groups. Participants with an EP >2% had a shorter ICU length of stay (OR=12.13, p=0.001) than those with an EP ≤2%, while an AEC >300 cells/μL was not associated with any in-ICU outcomes.
Conclusions The results of this study have significant clinical implications and should be considered when making treatment decisions for the management of patients with COPD and CAP requiring IMV and ICU admission.
Objectives
The clinical implications of blood eosinophil level in patients with chronic obstructive pulmonary disease (COPD) and community-acquired pneumonia (CAP) requiring invasive mechanical ventilation (IMV) and intensive care unit (ICU) admission are still unknown. Thus, this study aimed to compare the features of such patients with and without blood eosinophilia.
Design
This was a retrospective case–control study.
Setting
An ICU of a medical centre in central Taiwan.
Participants
A total of 262 patients with COPD and CAP requiring IMV and ICU admission.
Results
Of all participants (n=262), 32 (12.2%) had an eosinophil percentage (EP) >2% and 169 (64.5%) had an absolute eosinophil count (AEC) >300 cells/µL. Regardless of whether 2% or 300 cells/µL was used as a cut-off value, the eosinophilia group were slightly older (years) (82.9±5.4 vs 78.1±9.1, p=0.000 and 79.2±8.4 vs 77.6±9.6, p=0.246, respectively), and had a higher forced expiratory volume in 1 s/forced vital capacity (%) (56.0±8.0 vs 51.3±11.6, p=0.005 and 53.1±11.2 vs 49.5±11.2, p=0.013, respectively), less severe spirometric classification (p=0.008 and p=0.001, respectively), and lower white cell count 10 ⁹ /L (8.8±3.2 vs 11.1±4.9, p=0.009 and 10.3±4.4 vs 11.8±5.3, p=0.017, respectively) than the non-eosinophilia group. The bacteriology of endotracheal aspirates showed that Pseudomonas aeruginosa and other gram-negative bacilli were the most common organisms in all study groups. Participants with an EP >2% had a shorter ICU length of stay (OR=12.13, p=0.001) than those with an EP ≤2%, while an AEC >300 cells/µL was not associated with any in-ICUoutcomes.
Conclusions
The results of this study have significant clinical implications and should be considered when making treatment decisions for the management of patients with COPD and CAP requiring IMV and ICU admission.
Background: Inhaled corticosteroids are commonly prescribed for patients with severe COPD. They have been associated with increased risk of pneumonia but not with increased pneumonia-associated or overall mortality.
Methods: To further examine the effects of inhaled corticosteroids on pneumonia incidence, and mortality in COPD patients, we searched for potentially relevant articles in PubMed, Medline, CENTRAL, EMBASE, Scopus, Web of Science and manufacturers’ web clinical trial registries from 1994 to February 4, 2014. Additionally, we checked the included and excluded studies’ bibliographies. We subsequently performed systematic review and meta-analysis of included randomized controlled trials and observational studies on the topic.
Results: We identified 38 studies: 29 randomized controlled trials and nine observational studies. The estimated unadjusted risk of pneumonia was increased in randomized trials: RR 1.61; 95% CI 1.35–1.93, p < 0.001; as well as in observational studies: OR 1.89; 95% CI 1.39–2.58, p < 0·001. Six randomized trials and seven observational studies were useful in estimating unadjusted risk of pneumonia -case-fatality: RR 0.91; 95% CI 0.52–1.59, p = 0.74; and OR 0.72; 95% CI 0.59–0.88, p = 0.001, respectively. Twenty-nine randomized trials and six observational studies allowed estimation of unadjusted risk of overall mortality: RR 0.95; 95% CI 0.85–1.05, p=0.31; and OR 0.79; 95% CI 0.65–0.97, p=0.02, respectively.
Conclusions: Despite a substantial and significant increase in unadjusted risk of pneumonia associated with inhaled corticosteroid use, pneumonia fatality and overall mortality were found not to be increased in randomized controlled trials and were decreased in observational studies.
OBJECTIVE[|]Chronic Obstructive Pulmonary Disease (COPD) disease is characterized with acute exacerbation. Exacerbations are manifested with dyspnea and increased volume and purulence of sputum. Treatment may require the use of bronchodilators and antibiotics. With
an increase in airflow restriction it is reported to also increase the risk of exacerbations. Acute exacerbations decrease the quality of life of the patients, cause significant morbidity, mortality and economic hardship. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) group classified the COPD patients from 1 to 4. Number of exacerbation is 0.7-0.9 in GOLD 2 and 1.2-2.0 in GOLD 4 per year. The most common bacterial pathogens for acut exacerbation of COPD are Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, respectively. Pseudomonas aeruginosa is the more important agent for GOLD3 and GOLD4 COPD patients. The rising antimicrobial resistance to P. aeruginosa strains is a problem in the treatment. For the treatment of infection, antibiotic susceptability
pattern knowledge before starting empiric therapy may improve effectiveness. The sputum culture and antibiotic resistance tests should be performed if the patient has failed to respond to empirical antibiotic treatment. For this reason, in the current study we aimed to determine resistance patterns in P. aeruginosa strains isolated from the sputum with acute exacerbation of COPD patients in our hospital.[¤]METHODS[|]Patients who were admitted to Trabzon Ahi Evren Chest and Cardiovascular Surgery Training
and Research Hospital, with acute exacerbation of COPD between June 2007 and December 2010, had their sputum culture results reviewed. The results of antibiotics susceptibilities test in 78 P. aeruginosa strains isolated from sputum were evaluated retrospectively.
For typing and antibiotic susceptibility of isolates the Phoenix bacterial identification system (Becton Dickinson, USA) was used.[¤]RESULTS[|]The antibiotic resistance rates of P. aeruginosa were 42.3% for cefepime, 41% for levofloxacin, 38.7% for ciprofloxacin, 29.4% for ceftazidime, 21.7% for cefoperazone / sulbactam, 17.9% for gentamicin, 17.9% for piperacillin / tazobactam, 8.9% for imipenem, 5.1% for amikacin and 2.5% for meropenem. Twenty eight (35.9%) of the isolates were found to be sensitive to all of these antibiotics. Forty six (58.9%) of the patients had steroid and 56 (71.8%) of the patients had broad-spectrum antibiotic use.[¤]CONCLUSION[|]In acute exacerbations of chronic obstructive pulmonary disease, the inspection of antibiotic susceptibility of Pseudomonas infection would be beneficial for patient's health and the country's economy.[¤]
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Patients with COPD are at increased risk for community-acquired pneumonia (CAP). COPD has been reported as a comorbidity in at least one third of the hospitalized patients with CAP. There is a controversy that the presence of concomitant COPD and CAP is associated with a greater risk of death when compared to either condition alone. Risk factors, clinical and immunological characteristics, microbiological etiology, as well as prognosis and treatment of COPD patients with CAP are reviewed in this article.
Inhaled corticosteroids are commonly prescribed for patients with severe COPD. Although their use improves quality of life and reduces exacerbations, it is associated with increased risk of pneumonia. Curiously, their use has not been associated with increased risk of pneumonia-related or overall mortality. We review pertinent literature to further explore the effects of inhaled corticosteroids on incident pneumonia and mortality in patients with COPD. The association of use of inhaled corticosteroids and incident pneumonia is substantial, and has been present in the majority of the studies on the topic. This includes both randomized controlled trials as well as observational studies. However, all of the studies have substantial risk of bias. Most randomized trials are limited by lack of systematic ascertainment of pneumonia; they depended on adverse event reporting. Many observational studies included proper radiographic assessment of pneumonia, but they are limited by their retrospective, observational design. The unadjusted higher risk of pneumonia is associated with longer duration of use, more potent ICS compounds, and higher doses. That implies a dose-effect relationship. Unlike pneumonia, mortality is a precise outcome. Despite the robust association of inhaled corticosteroid use with increased risk of pneumonia, all studies find either no difference or a reduction in pulmonary-related and overall mortality associated with the use of inhaled corticosteroids. These observations suggest a double-effect of inhaled corticosteroids, i.e. an adverse effect plus an unexplained mitigating effect.
The common cold is most often a result of human rhinovirus (HRV) infection. Common cold symptoms including rhinorrhea and nasal obstruction frequently occur during HRV infection of the upper respiratory tract. Conversely, HRV may also infect the epithelial cells of the lower respiratory tract. Symptom severity associated with HRV infection ranges from mild to potentially serious depending on a person’s susceptibility and pre-existing condition, such as chronic obstructive pulmonary disease. An over active host immune response is believed to be the primary contributor to HRV pathogenesis. Enhanced activity of various host cell cytokines and granulocytes mediate specific cellular pathways inducing many of the symptoms associated with HRV infection. There are over 100 serotypes of HRV which can be further categorized based on the specific characteristics of each type. The two main categories of HRV consist of the major and minor groups. The unique host cell receptor is the distinguishing factor between these two groups. Yet, these viruses may also differ in mechanism of infection and replication. Due to the high frequency of hospital and clinical visits and the corresponding economic burden, novel therapies are of interest. Several different treatment options varying from herbal remedies to anti-viral drugs have been studied. However, the vast number of HRV serotypes complicates the progress of developing a universal treatment for attenuating HRV infection.
To explore the risk factors for hospitalization case fatality of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
A retrospective review of medical records was performed for 182 hospitalized AECOPD patients at Nanfang Hospital from January 2010 to August 2012. Their general information, condition in stable stage, the results of spirometry, blood routine test, blood gas analysis and C-reactive protein (CRP) were collected and analyzed. The risk factors for mortality were analyzed by multivariable Logistic regression.
Among them, 42 died during hospitalization. Univariate analysis revealed that 8 factors had significant differences between two groups (all P < 0.05): high exacerbation risk (death vs improvement group, 90.4% vs 70.0%) , low peripheral absolute lymphocyte count (73.8% vs 47.1%), high CRP (50.0% vs 17.1%), concurrent anemia (50.0% vs 27.1%), hypoproteinemia (71.4% vs 46.4%), hypercapnia (64.3% vs 30.7%), chronic pulmonary heart disease (76.1% vs 40.7%) and ischemic heart disease (19.0% vs 7.0%). By multiple Logistic regression analysis, high CRP (OR = 3.226, P = 0.009), hypercapnia (OR = 2.928, P = 0.013), chronic pulmonary heart disease (OR = 2.510, P = 0.045), low peripheral absolute lymphocyte count (OR = 2.488, P = 0.045) were the independent risk factors for hospitalization case fatality of AECOPD patients.
Low peripheral absolute lymphocyte count, high CRP, hypercapnia and chronic pulmonary heart disease were the independent risk factors for mortality in hospitalized AECOPD patients.
Chronic obstructive pulmonary disease (COPD) is a chronic disease causing increasing healthcare costs worldwide. Another respiratory disease causing high costs and morbidity is community-acquired pneumonia (CAP). Because of the constant growth in the population with both diseases (CAP and COPD), analyzing their clinical characteristics is important. Several cellular factors are known to contribute to differences in clinical expression: some lead to COPD exacerbations while others lead to symptoms of pneumonia. The use of new biomarkers (procalcitonin, pro-adrenomedullin and copeptin) help to distinguish among these clinical pictures. To decrease morbidity and mortality, clinical guidelines on antibiotic therapy must be followed and this therapy should be prescribed to patients with CAP and COPD. There are also prevention measures such as the pneumococcal vaccine whose role in the prevention of pneumococcal CAP should be further studied. The present review aims to elucidate some of the above-mentioned issues.
Methods: Eighty episodes of hospitalization in 65 CAP-COPD patients, and 111 episodes of hospitalization in 82 AE-COPD patients were included in this study. The baseline characteristics, clinical presentations, potential bacterial pathogens and clinical outcomes in these patients were retrospectively reviewed and compared. Results: No significant differences were found between the two groups in parameters related to COPD and co-morbidities, except a higher rate of male among CAP-COPD patients. Clinical presentations by symptoms and laboratory findings on admission were significantly more severe in CAP-COPD patients, who showed higher rates of fever and crepitation, but less wheezing than AE-COPD patients. S. pneumoniae and P. aeruginosae were the most common bacterial pathogens in both groups. With no difference in the overall hospital mortality between both groups, the mean length of hospital stay was significantly longer in the CAP-COPD patients than in AE-COPD patients (15.3 vs. 9.8 days, respectively, p
Respiratory exacerbations are characteristic of chronic obstructive pulmonary disease (COPD) and are associated with poorer health outcomes. The seasonal influenza virus is a common viral pathogen in COPD exacerbations. Prevention of influenza-related exacerbations is therefore important. The objectives of this review article are to summarize current international guidelines regarding seasonal influenza vaccination in COPD, and then to discuss two important issues relating to influenza vaccination in COPD: the low uptake of influenza vaccination and the conflicting nature of the evidence regarding its effectiveness. Despite strong universal recommendation for a broad influenza vaccination strategy in COPD, influenza vaccine uptake in COPD is low internationally, and studies examining vaccine effectiveness in COPD show mixed results. Demonstrating and disseminating evidence of the potential merits of influenza vaccination in COPD is necessary before we can confidently and successfully pursue policies of mass vaccination.
Streptococcus pneumoniae, the most common cause of community-acquired pneumonia, remains a major cause of morbidity and mortality worldwide. The presence of chronic respiratory illness is a major risk factor for pneumonia, and smoking (the most common cause of chronic obstructive pulmonary disease) is also an important risk factor for pneumonia and invasive pneumococcal disease. There are currently three established approaches to antipneumococcal vaccination: capsular polysaccharide pneumococcal vaccines (recommended for adults and some children at risk), protein-polysaccharide conjugate pneumococcal vaccines (classically recommended for infants and young children and currently under evaluation for adults aged 50 years or older for the prevention of invasive disease) and experimental protein-based pneumococcal vaccines (under investigation in animal models). Although patients with chronic respiratory diseases are commonly described as an at-risk population for pneumococcal infections, studies on pneumococcal vaccination efficacy in such patients are very limited and vaccination effectiveness remains controversial. This paper reviews available data on the efficacy and effectiveness of polysaccharide pneumococcal vaccination among adults with chronic respiratory diseases.
To assess the associations of oral hygiene and periodontal health with chronic obstructive pulmonary disease (COPD) exacerbations.
In total, 392 COPD patients were divided into frequent and infrequent exacerbation (≥2 times and <2 times in last 12 months) groups. Their lung function and periodontal status were examined. Information on oral hygiene behaviours was obtained by interview.
In the univariate analysis, fewer remaining teeth, high plaque index (PLI) scores, low tooth brushing times, and low regular supra-gingival scaling were significantly associated with COPD exacerbations (all p-values <0.05). After adjustment for age, gender, body mass index, COPD severity and dyspnoea severity, the associations with fewer remaining teeth (p = 0.02), high PLI scores (p = 0.02) and low tooth brushing times (p = 0.008) remained statistically significant. When stratified by smoking, fewer remaining teeth (OR = 2.05, 95% CI: 1.04-4.02) and low tooth brushing times (OR = 4.90, 95% CI: 1.26-19.1) among past smokers and high PLI scores (OR = 3.43, 95% CI: 1.19-9.94) among never smokers were significantly associated with COPD exacerbations.
Fewer remaining teeth, high PLI scores, and low tooth brushing times are significant correlates of COPD exacerbations, indicating that improving periodontal health and oral hygiene may be a potentially preventive strategy against COPD exacerbations.
Rhinoviruses and coronaviruses cause significant morbidity in immunocompetent people of all ages and in patients with underlying chronic medical or immunosuppressed conditions. Newer diagnostic tests, such as polymerase chain reaction (PCR), have expanded our understanding of these respiratory viruses in clinical infections. These sensitive diagnostic tests have been used to describe new members of these virus families, such as human rhinovirus C (HRVC) and human coronavirus NL-63 (HCoV-NL63). The epidemiology of these newly described viruses will help us develop better intervention strategies.
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death among adults in Brazil.
To evaluate the mortality and hospitalisation trends in Brazil caused by COPD during the period 1996-2008.
We used the health official statistics system to obtain data about mortality (1996-2008) and morbidity (1998-2008) due to COPD and all respiratory diseases (tuberculosis: codes A15-16; lung cancer: code C34, and all diseases coded from J40 to 47 in the 10th Revision of the International Classification of Diseases) as the underlying cause, in persons aged 45-74 years. We used the Joinpoint Regression Program log-linear model using Poisson regression that creates a Monte Carlo permutation test to identify points where trend lines change significantly in magnitude/direction to verify peaks and trends.
The annual per cent change in age-adjusted death rates due to COPD declined by 2.7% in men (95%CI -3.6 to -1.8) and -2.0% (95%CI -2.9 to -1.0) in women; and due to all respiratory causes it declined by -1.7% (95%CI 2.4 to -1.0) in men and -1.1% (95%CI -1.8 to -0.3) in women. Although hospitalisation rates for COPD are declining, the hospital admission fatality rate increased in both sexes.
COPD is still a leading cause of mortality in Brazil despite the observed decline in the mortality/hospitalisation rates for both sexes.
Antimicrobial resistance is a global problem and the prevalence is high in many Asian countries.
A prospective observational study of the prevalence of bacterial pathogens and their antimicrobial susceptibilities in patients with acute exacerbations of chronic bronchitis (AECB) was conducted in Indonesia, Philippines, Korea, Thailand, Malaysia, Taiwan and Hong Kong from August 2006 to April 2008. The diagnosis of AECB was based on increased cough and worsening of two of following: dyspnoea, increased sputum volume or purulence. Patients who had taken antibiotics within 72 h of presentation were excluded. All bacterial strains were submitted to a central laboratory for re-identification and antimicrobial susceptibility testing to 16 antimicrobial agents according to Clinical and Laboratory Standards Institute.
Four hundred and seven isolates were identified among 447 patients of AECB. The most frequent organisms isolated were Klebsiella pneumoniae and associated species (n = 91 + 17), Haemophilus influenzae (n = 71), Pseudomonas aeruginosa (n = 63), Streptococcus pneumoniae (n = 32), Acinetobacter baumannii (n = 22) and Moraxella catarrhalis (n = 21). According to Clinical and Laboratory Standards Institute susceptibility breakpoints, 85.7% and >90% of these pathogens were susceptible to levofloxacin and cefepime respectively. Other options with overall lower susceptibilities include imipenem, ceftazidime, ceftriaxone and amoxicillin/clavulanate.
Gram-negative bacteria including Klebsiella spp., P. aeruginosa and Acinetobacter spp. constitute a large proportion of pathogens identified in patients with AECB in some Asian countries. Surveillance on the local prevalence and antibiotic resistance of these organisms is important in guiding appropriate choice of antimicrobials in the management of AECB.
Over the past 15 years, no fewer than ten meta-analyses or systematic literature reviews of the efficacy of pneumococcal polysaccharide vaccine in adults have been conducted, including one specifically in chronic obstructive pulmonary disease patients. Their general conclusion is that it is effective in preventing invasive infections, but no conclusions can be drawn for high-risk patients (owing to a highly polymorphic population). Opinions are divided as to its efficacy in pneumonia, with the studies being too heterogeneous to carry sufficient statistical weight. Most conclude that there is no impact on mortality. Chronic obstructive pulmonary disease patients are frequently described as an at-risk population, but controlled studies in such patients are very limited, leaving only case-control or cohort studies to provide information on which to base any decision. The aim of this article is first to discuss the place of pneumococcal polysaccharide vaccination in this risk population, which is increasing in prevalence and in which pneumococcal infections play a considerable role. Pending other vaccines, the polysaccharide vaccine is currently the only preventive approach that has demonstrated an effect, even if it does not match up to expectations. The possibilities of alternative vaccines, such as conjugate vaccines in the near future and perhaps protein vaccines at a later date, will be considered.
The role of viruses in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) needs further elucidation. The aim of the present study was to evaluate the molecular epidemiology of viral pathogens in AECOPD. Patients presenting to the Emergency Room with AECOPD needing hospitalization were recruited. Oropharyngeal and sputum samples were collected in order to perform microarrays-based viral testing for the detection of respiratory viruses. A total of 200 (100%) patients were analyzed and from them in 107 (53.5%) a virus was detected. The commonest identified viruses were the human Respiratory Syncytial Virus (subtypes A and B) (40.5%), influenza virus (subtypes A, B, C) (11%), rhinovirus (8%) and human Parainfluenza Virus (subtypes A and B) (7.5%). A bacterial pathogen was isolated in 27 (14%) patients and a dual infection due to a bacterial and a viral pathogen was recognised in 14/107 patients. Patients with AECOPD and a viral infection had a lengthier hospital stay (9.2 ± 4.6 vs 7.6 ± 4.3, p < 0.01) while the severity of the disease was no related with significant differences among the groups of the study population. In conclusion, the isolation of a virus was strongly associated with AECOPD in the examined population. The stage of COPD appeared to have no relation with the frequency of the isolated viruses while dual infection with a viral and a bacterial pathogen was not rare.
Exacerbations occur commonly in patients with moderate or severe chronic obstructive pulmonary disease (COPD) but factors affecting their severity and frequency or effects on quality of life are unknown. We measured daily peak expiratory flow rate (PEFR) and daily respiratory symptoms for 1 yr in 70 COPD patients (52 male, 18 female, mean age [+/- SD] 67.5 +/- 8.3 yr, FEV1 1.06 +/- 0.45 L, FVC 2.48 +/- 0.82 L, FEV1/FVC 44 +/- 15%, FEV1 reversibility 6.7 +/- 9.1%, PaO2 8.8 +/- 1.1 kPa). Quality of life was measured by the St. George's Respiratory Questionnaire (SGRQ). Exacerbations (E) were assessed at acute visit (reported exacerbation) or from diary card data each month (unreported exacerbation). In 61 (87%) patients there were 190 exacerbations (median 3; range, 1 to 8) of which 93 (51%) were reported. There were no differences in major symptoms (increase in dyspnea, sputum volume, or purulence) or physiological parameters between reported and unreported exacerbations. At exacerbation, median peak flow fell by an average of 6.6 L/min (p = 0.0003). Using the median number of exacerbations as the cutoff point, patients were classified as infrequent exacerbators (E = 0 to 2) or frequent exacerbators (E = 3 to 8). The SGRQ Total and component scores were significantly worse in the group that had frequent exacerbations: SGRQ Total score (mean difference = 14.8, p < 0.001), Symptoms (23.1, p < 0.001), Activities (12.2, p = 0.003), Impacts (13.9, p = 0.002). However there was no difference between frequent and infrequent exacerbators in the fall in peak flow at exacerbation. Factors predictive of frequent exacerbations were daily cough (p = 0.018), daily wheeze (p = 0.011), and daily cough and sputum (p = 0.009) and frequent exacerbations in the previous year (p = 0.001). These findings suggest that patient quality of life is related to COPD exacerbation frequency.
Patients with chronic obstructive pulmonary disease (COPD) are prone to frequent exacerbations which are a significant cause of morbidity and mortality. Stable COPD patients often have lower airway bacterial colonisation which may be an important stimulus to airway inflammation and thereby modulate exacerbation frequency.
Twenty nine patients with COPD (21 men, 16 current smokers) of mean (SD) age 65.9 (7.84) years, forced expiratory volume in 1 second (FEV(1)) 1.06 (0.41) l, FEV(1) % predicted 38.7 (15.2)%, FEV(1)/FVC 43.7 (14.1)%, inhaled steroid dosage 1.20 (0.66) mg/day completed daily diary cards for symptoms and peak flow over 18 months. Exacerbation frequency rates were determined from diary card data. Induced sputum was obtained from patients in the stable state, quantitative bacterial culture was performed, and cytokine levels were measured.
Fifteen of the 29 patients (51.7%) were colonised by a possible pathogen: Haemophilus influenzae (53.3%), Streptococcus pneumoniae (33.3%), Haemophilus parainfluenzae (20%), Branhamella catarrhalis (20%), Pseudomonas aeruginosa (20%). The presence of lower airway bacterial colonisation in the stable state was related to exacerbation frequency (p=0.023). Patients colonised by H influenzae in the stable state reported more symptoms and increased sputum purulence at exacerbation than those not colonised. The median (IQR) symptom count at exacerbation in those colonised by H influenzae was 2.00 (2.00-2.65) compared with 2.00 (1.00-2.00) in those not colonised (p=0.03). The occurrence of increased sputum purulence at exacerbation per patient was 0.92 (0.56-1.00) in those colonised with H influenzae and 0.33 (0.00-0.60) in those not colonised (p=0.02). Sputum interleukin (IL)-8 levels correlated with the total bacterial count (rho=0.459, p=0.02).
Lower airway bacterial colonisation in the stable state modulates the character and frequency of COPD exacerbations.
Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are a common cause of hospital admission. Many exacerbations are believed to be due to upper and/or lower respiratory tract viral infections, but the incidence of these infections in patients with COPD is still undetermined.
Respiratory syncytial virus (RSV), influenza A and B, parainfluenza 3, and picornaviruses were detected by nested reverse transcription polymerase chain reaction (RT-PCR) in upper (nasal lavage) and lower respiratory tract specimens (induced sputum). In a 2:1 case-control set up, 85 hospitalised patients with AE-COPD and 42 patients with stable COPD admitted for other medical reasons were studied.
Respiratory viruses were found more often in sputum and nasal lavage of patients with AE-COPD (48/85, 56%) than in patients with stable COPD (8/42, 19%, p<0.01). The most common viruses were picornaviruses (21/59, 36%), influenza A (15/59, 25%), and RSV (13/59, 22%). When specimens were analysed separately, this difference was seen in induced sputum (exacerbation 40/85 (47%) v stable 4/42 (10%), p<0.01) but was not significant in nasal lavage (exacerbation 26/85 (31%) v stable 7/42 (17%), p=0.14). In patients with AE-COPD, fever was more frequent in those in whom viruses were detected (12/48, 25%) than in those in whom viruses were not detected (2/37, 5%, p=0.03).
Viral respiratory pathogens are found more often in respiratory specimens of hospitalised patients with AE-COPD than in control patients. Induced sputum detects respiratory viruses more frequently than nasal lavage in these patients. These data indicate that nasal lavage probably has no additional diagnostic value to induced sputum in cross-sectional studies on hospitalised patients with AE-COPD and that the role of viral infection in these patients is still underestimated.
The purpose of our study was to analyze prognostic factors associated with mortality for patients with severe community-acquired pneumonia (CAP).
We conducted a prospective multicenter study including all patients with CAP admitted to the intensive care unit during a 15-month period in 33 Spanish hospitals. Admission data and data on the evolution of the disease were recorded. Multivariate analysis was performed using the SPSS statistical package (SPSS).
A total of 529 patients with severe CAP were enrolled; the mean age (+/-SD) was 59.9+/-16.1 years, and the mean Acute Physiology and Chronic Health Evaluation (APACHE) II score (+/-SD) was 18.9+/-7.4. Overall mortality among patients in the intensive case unit was 27.9% (148 patients). The rate of adherence to Infectious Diseases Society of America (IDSA) guidelines was 57.8%. Significantly higher mortality was documented among patients with nonadherence to treatment (33.2% vs. 24.2%). Multivariate analysis identified age (odds ratio [OR], 1.7), APACHE II score (OR, 4.1), nonadherence to IDSA guidelines (OR, 1.6), and immunocompromise (OR, 1.9) as the variables present at admission to the intensive care unit that were independently associated with death in the intensive care unit. In 15 (75%) of 20 cases of Pseudomonas aeruginosa infection, the antimicrobial treatment at admission was inadequate (including 8 of 15 cases involving patients with adherence to IDSA guidelines). Chronic obstructive pulmonary disease (OR, 17.9), malignancy (OR, 11.0), previous antibiotic exposure (OR, 6.2), and radiographic findings demonstrating rapid spread of disease (OR, 3.9) were associated with P. aeruginosa pneumonia.
Better adherence to IDSA guidelines would help to improve survival among patients with severe CAP. Pseudomonas coverage should be considered for patients with chronic obstructive pulmonary disease, malignancy, or recent antibiotic exposure.
Patients with chronic obstructive pulmonary disease (COPD) who develop community-acquired pneumonia (CAP) may experience worse clinical outcomes. However, COPD is not included as a distinct diagnosis in validated instruments that predict mortality in patients with CAP. The aim of the present study was to evaluate the impact of COPD as a comorbid condition on 30- and 90-day mortality in CAP patients. A retrospective observational study was conducted at two hospitals. Eligible patients had a discharge diagnosis and radiological confirmation of CAP. Among 744 patients with CAP, 215 had a comorbid diagnosis of COPD and 529 did not have COPD. The COPD group had a higher mean pneumonia severity index score (105+/-32 versus 87+/-34) and were admitted to the intensive care unit more frequently (25 versus 18%). After adjusting for severity of disease and processes of care, CAP patients with COPD showed significantly higher 30- and 90-day mortality than non-COPD patients. Chronic obstructive pulmonary disease patients hospitalised with community-acquired pneumonia exhibited higher 30- and 90-day mortality than patients without chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease should be evaluated for inclusion in community-acquired pneumonia prediction instruments.
Long-acting beta-agonists and inhaled corticosteroids are used to treat chronic obstructive pulmonary disease (COPD), but their effect on survival is unknown.
We conducted a randomized, double-blind trial comparing salmeterol at a dose of 50 microg plus fluticasone propionate at a dose of 500 microg twice daily (combination regimen), administered with a single inhaler, with placebo, salmeterol alone, or fluticasone propionate alone for a period of 3 years. The primary outcome was death from any cause for the comparison between the combination regimen and placebo; the frequency of exacerbations, health status, and spirometric values were also assessed.
Of 6112 patients in the efficacy population, 875 died within 3 years after the start of the study treatment. All-cause mortality rates were 12.6% in the combination-therapy group, 15.2% in the placebo group, 13.5% in the salmeterol group, and 16.0% in the fluticasone group. The hazard ratio for death in the combination-therapy group, as compared with the placebo group, was 0.825 (95% confidence interval [CI], 0.681 to 1.002; P=0.052, adjusted for the interim analyses), corresponding to a difference of 2.6 percentage points or a reduction in the risk of death of 17.5%. The mortality rate for salmeterol alone or fluticasone propionate alone did not differ significantly from that for placebo. As compared with placebo, the combination regimen reduced the annual rate of exacerbations from 1.13 to 0.85 and improved health status and spirometric values (P<0.001 for all comparisons with placebo). There was no difference in the incidence of ocular or bone side effects. The probability of having pneumonia reported as an adverse event was higher among patients receiving medications containing fluticasone propionate (19.6% in the combination-therapy group and 18.3% in the fluticasone group) than in the placebo group (12.3%, P<0.001 for comparisons between these treatments and placebo).
The reduction in death from all causes among patients with COPD in the combination-therapy group did not reach the predetermined level of statistical significance. There were significant benefits in all other outcomes among these patients. (ClinicalTrials.gov number, NCT00268216 [ClinicalTrials.gov].).
BACKGROUND AND STUDY OBJECTIVES: The range and relative impact of microbial pathogens, particularly viral pathogens, as a cause of community-acquired pneumonia (CAP) in hospitalized adults has not received much attention. The aim of this study was to determine the microbial etiology of CAP in adults and to identify the risk factors for various specific pathogens.
We prospectively studied 176 patients (mean [+/- SD] age, 65.8 +/- 18.5 years) who had hospitalized for CAP to identify the microbial etiology. For each patient, sputum and blood cultures were obtained as well as serology testing for Mycoplasma pneumoniae and Chlamydophila pneumoniae, urinary antigen testing for Legionella pneumophila and Streptococcus pneumoniae, and a nasopharyngeal swab for seven respiratory viruses.
Microbial etiology was determined in 98 patients (55%). S pneumoniae (49 of 98 patients; 50%) and respiratory viruses (32%) were the most frequently isolated pathogen groups. Pneumococcal pneumonia was associated with tobacco smoking of > 10 pack-years (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.2 to 5.4; p = 0.01). Respiratory viruses were isolated more often in fall or winter (28%; p = 0.011), and as an exclusive etiology tended to be isolated in patients >/= 65 years of age (20%; p = 0.07). Viral CAP was associated with antimicrobial therapy prior to hospital admission (OR, 4.5; 95% CI, 1.4 to 14.6).
S pneumoniae remains the most frequent pathogen in adults with CAP and should be covered with empirical antimicrobial treatment. Viruses were the second most common etiologic agent and should be tested for, especially in fall or winter, both in young and elderly patients who are hospitalized with CAP.
The aetiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) is heterogeneous and still under discussion. Serological studies have suggested that Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila may play a role in acute exacerbations of COPD. The presence of these atypical pathogens in sputum samples was investigated in patients with stable COPD and with acute exacerbations of COPD using real-time PCR. The present study was part of a randomised, double-blind, single-centre study and a total of 248 sputum samples from 104 COPD patients were included. In total, 122 samples obtained during stable disease (stable-state sputa) and 126 samples obtained during acute exacerbations of COPD (exacerbation sputa) were tested. Of the 122 stable-state sputa, all samples were negative for M. pneumoniae and C. pneumoniae DNA, whereas one sample was positive for Legionella non-pneumophila DNA. Of the 126 exacerbation sputa, all samples were negative for M. pneumoniae and C. pneumoniae DNA, whereas one sample was positive for Legionella non-pneumophila DNA. The possible relationship between the presence of atypical pathogens and the aetiology of acute exacerbations in chronic obstructive pulmonary disease was investigated in patients with stable disease and in those with acute exacerbations using real-time PCR. No indication was found of a role for Legionella spp., Chlamydia pneumoniae or Mycoplasma pneumoniae in stable, moderately severe chronic obstructive pulmonary disease and in its exacerbations.
Viral respiratory infections may precipitate acute exacerbations of COPD (AECOPD). However, little is known about viral etiology related to AECOPD in Asia. We aimed to study the viral etiology of AECOPD in Hong Kong.
Patients admitted to an acute hospital in Hong Kong with AECOPD were recruited prospectively from May 1, 2004, to April 30, 2005. Nasopharyngeal aspirate was collected and assessed by polymerase chain reaction (PCR) and viral culture. Spirometry was performed in the stable phase at 2 to 3 months after hospital discharge.
There were 262 episodes of AECOPD among 196 patients (mean age, 75.7 +/- 7.7 years [+/- SD]; 160 men). Mean FEV(1) was 39.6 +/- 18.9% of predicted normal, and FEV(1)/FVC ratio was 58.0 +/- 15.2%. Fifty-eight episodes (22.1%) yielded positive viral PCR results. The viruses identified were influenza A (7.3%), coronavirus OC43 (4.6%), rhinovirus (3.1%), influenza B (2.7%), and respiratory syncytial virus (2.3%). The diagnostic yield of viral identification by PCR was 2.7 times higher than that based on conventional viral culture. The rates of identifying a positive viral etiology by PCR were similar among the subjects with FEV(1) >or= 50%, >or= 30 to 50%, and < 30% of predicted normal. Viral infection appeared to have no effect on subsequent readmissions or mortality rate over a study period of 1 year
Influenza A and two less-attended viruses, coronavirus OC43 and rhinovirus, were the common etiologic agents in patients hospitalized with AECOPD in Hong Kong. These should be considered in developing diagnostic and intervening strategies pertaining to AECOPD.
Respiratory tract infections can be caused by a heterogeneous group of viruses and bacteria that produce similar clinical presentations. Specific diagnosis therefore relies on laboratory investigation. This study developed and evaluated five groups of multiplex nested PCR assays that could simultaneously detect 21 different respiratory pathogens: influenza A virus (H1N1, H3N2, and H5N1); influenza B virus; parainfluenza virus types 1, 2, 3, 4a, and 4b; respiratory syncytial virus A and B; human rhinoviruses; human enteroviruses; human coronaviruses OC43 and 229E; severe acute respiratory syndrome coronavirus; human metapneumoviruses; Mycoplasma pneumoniae; Chlamydophila pneumoniae; Legionella pneumophila; and adenoviruses (A to F). These multiplex nested PCRs adopted fast PCR technology. The high speed of fast PCR (within 35 min) greatly improved the efficiency of these assays. The results show that these multiplex nested PCR assays are specific and more sensitive (100- to 1,000-fold) than conventional methods. Among the 303 clinical specimens tested, the multiplex nested PCR achieved an overall positive rate of 48.5% (95% confidence interval [CI], 42.9 to 54.1%), which was significantly higher than that of virus isolation (20.1% [95% CI, 15.6 to 24.6%]) and that of direct detection by immunofluorescence assay (13.5% [95% CI, 9.7 to 17.4%]). The improved sensitivity was partly due to the higher sensitivity of multiplex nested PCR than that of conventional methods in detecting cultivatable viruses. Moreover, the ability of the multiplex nested PCR to detect noncultivatable viruses, particularly rhinoviruses, coronavirus OC43, and metapneumoviruses, contributed a major gain (15.6%) in the overall positive rate. In conclusion, rapid multiplex nested PCR assays can improve the diagnostic yield for respiratory infections to allow prompt interventive actions to be taken.
The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
Study objective: To describe and compare the background, clinical manifestations, disease course, and infectious etiologies of pneumonic acute exacerbations (PNAE) vs nonpneumonic acute exacerbations (NPAE) of COPD. Design: A prospective, observational study. Setting: A tertiary university medical center in southern Israel. Patients: Twenty-three hospitalizations for PNAE and 217 hospitalizations for NPAE were included in the study. Paired sera were obtained for each of the hospitalizations and were tested serologically for 12 pathogens. Only a significant change in antibody titers or levels was considered diagnostic. Results: No significant differences were found between the two groups for any of the parameters related to COPD or comorbidity. The clinical type of the exacerbation was not significantly different between the groups. Compared to NPAE, patients with PNAE had lower PO2 values at hospital admission (p 0.004) but higher rates of abrupt onset (p 0.005), ICU admissions (p 0.006), invasive mechanical ventilation (p 0.01), mortality (p 0.007), and longer hospital stay (p 0.001). In 22 PNAE hospitalizations (96%) and in 153 NPAE hospitalizations (71%), at least one infectious etiology was identified (p 0.001). Mixed infection was found in 13 patients with PNAE (59%) and in 59 patients with NPAE (39%; not significant [NS]). Viral etiology was identified in 18 patients with PNAE (78%) compared with 99 patients with NPAE (46%; p 0.003). Pneumococcal etiology was found in 10 patients with PNAE (43%) and in 38 patients with NPAE (18%; p 0.006). An atypical etiology was identified in 8 patients with PNAE (35%) and 64 patients with NPAE (30%; NS). Conclusions: Community-acquired pneumonia is common among patients hospitalized for an acute exacerbation of COPD and is generally manifested by more severe clinical and laboratory parameters. In PNAE, compared to NPAE, viral and pneumococcal etiologies are more common, but the rate of atypical pathogens is similar. The therapeutic significance of these findings should be investigated further. (CHEST 2002; 122:1264–1270)
Inhaled corticosteroids are commonly prescribed to patients with chronic obstructive pulmonary disease (COPD).
To examine whether these medications might be associated with an excess risk of pneumonia.
We conducted a nested case-control study within a cohort of patients with COPD from Quebec, Canada, over the period 1988-2003, identified on the basis of administrative databases linking hospitalization and drug-dispensing information. Each subject hospitalized for pneumonia during follow-up (case subjects) was age and time matched to four control subjects. The effect of the use of inhaled corticosteroids was assessed by conditional logistic regression, after adjusting for comorbidity and COPD severity.
The cohort included 175,906 patients with COPD of whom 23,942 were hospitalized for pneumonia during follow-up, for a rate of 1.9 per 100 per year, and matched to 95,768 control subjects. The adjusted rate ratio of hospitalization for pneumonia associated with current use of inhaled corticosteroids was 1.70 (95% confidence interval [CI], 1.63-1.77) and 1.53 (95% CI, 1.30-1.80) for pneumonia hospitalization followed by death within 30 days. The rate ratio of hospitalization for pneumonia was greatest with the highest doses of inhaled corticosteroids, equivalent to fluticasone at 1,000 microg/day or more (rate ratio, 2.25; 95% CI, 2.07-2.44). All-cause mortality was similar for patients hospitalized for pneumonia, whether or not they had received inhaled corticosteroids in the recent past (7.4 and 8.2%, respectively).
The use of inhaled corticosteroids is associated with an excess risk of pneumonia hospitalization and of pneumonia hospitalization followed by death within 30 days, among elderly patients with COPD.
A prospective study of community-acquired pneumonia in Hong Kong was carried out between January and December, 1988. Ninety adults (57 male) with a mean age of 57.3 years were admitted to the Prince of Wales Hospital with community-acquired pneumonia. The etiologic diagnosis of pneumonia was made in 37 cases (41 percent). Pneumococcal infection was diagnosed in 11 patients (12 percent). The same number of patients had pulmonary tuberculosis presenting as acute pneumonia. It could not be differentiated from other causes of pneumonia on clinical and radiologic grounds, although pleural effusion and upper lobe involvement were more common in patients with tuberculosis. Chlamydia species were identified in five patients (6 percent) and Mycoplasma pneumoniae was identified in three patients (3 percent). There was no case of Legionnaires' disease. The etiologic agent could not be identified in 59 percent of cases. The low incidence of etiologic diagnosis of community-acquired pneumonia was probably related to the widespread use of antibiotics in private practice. Tuberculosis is an important cause of community-acquired pneumonia in Hong Kong and this diagnosis should be considered in patients who fail to respond to first-line antibiotics.
The frequency of community-acquired pneumonia coupled with its mortality rate of 10 to 25% is of growing concern to clinicians. A prospective study of 67 patients with severe community-acquired pneumonia was carried out to determine the causative agents, the impact fore-knowledge of the etiology has on the outcome, the value of clinical and radiologic criteria in predicting the evolution, and the efficacy of empirical therapy. The study group included 45 men and 22 women (mean age: 56.8 +/- 16.6 yr), and 46.2% suffered from a concurrent debilitating disease. The cause of pneumonia was diagnosed in 32 cases, and the most common pathogens were Streptococcus pneumoniae (37.5%), Legionella pneumophila (21.8%), and gram-negative bacilli (25.0%). The fact that fungal infections were present in three patients and Pneumocystis carinii in one are worthy of note. The overall death rate was 20.8%. A fatal outcome was related to the age of the patient (p less than 0.05), the presence of debilitating disease (p = 0.026), and septic shock (p = 0.0009). Diagnosis of the causative agents did not aid in increasing the survival rate, but it did allow for better patient management. Most of the patients (85.1%) initiated on treatment with erythromycin plus tobramycin recovered, but only 68.4% of the subjects commenced on treatment with other therapeutics survived. Furthermore, it was necessary to modify the therapy of a greater percentage of the latter group (p less than 0.025). Gram-negative bacillary pneumonia was a frequent finding among the patients who did not recover, making empirical treatment with erythromycin plus third generation cephalosporins most advisable for severe cases of community-acquired pneumonia.
We studied all patients with community-acquired pneumonia who were admitted to our 800-bed adult acute care hospital from 1 November 1981 to 15 March 1987. The 719 patients had a mean age of 63.2 years; 18% were admitted from nursing homes, and 18% required ventilatory assistance as part of the therapy for pneumonia. Patients with nursing home-acquired pneumonia were significantly older; had a higher mortality (40% vs. 17%); were more likely to be admitted in January; were less likely to complain of cough, fever, anorexia, chills, headache, nausea, sore throat, myalgia, or arthralgia; and were more likely to be confused than those admitted from the community. Pneumonia of unknown etiology and aspiration pneumonia were more common and Mycoplasma pneumoniae infection less common among those with nursing home-acquired pneumonia. Streptococcus pneumoniae accounted for 58% of the 48 cases of bacteremia. None of the bacteremic patients received antibiotics before admission, compared with 34% of the nonbacteremic patients. Aerobic gram-negative rod bacteremia was not more frequent among nursing home patients than among those from the community. The overall mortality was 21% (8.5% for those less than 60 years of age and 28.6% for those greater than 60 years old). By multivariate analysis the following variables were significant predictors of mortality: number of lobes involved by the pneumonic process, number of antibiotics used to treat the pneumonia, age, admission from a nursing home, ventilatory support, and the number of complications that occurred while the patient was in the hospital.
The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
Community-acquired pneumonia (CAP) is an infectious illness that frequently motivates hospital admission when comorbid conditions are present. However, the epidemiology of CAP in relation to the underlying disease of the patients is not well known. We performed a prospective multicenter study with the aim of assessing the clinical characteristics, etiology, and outcome of chronic obstructive pulmonary disease (COPD) patients with CAP. Between October 1992 and December 1994 we studied 124 COPD patients (mean FEV1 40 +/- 11% of predicted, mean FVC/FEV1 49 +/- 10) admitted because of CAP to one of the participating centers. An attempt to obtain an etiologic diagnosis was performed by means of blood cultures (n = 123), sputum cultures (n = 97), pleural fluid cultures (n = 17), protected specimen brush samples (n = 41), percutaneous transthoracic needle aspiration (n = 41), and serology (n = 106). Etiologic diagnosis was achieved in 80 (64%) of cases, however, diagnosis based upon valid techniques was only possible in 73 (59%) cases. The main causal microorganisms were the following: Streptococcus pneumoniae in 32 (43%), Chlamydia pneumoniae in 9 (12%), Hemophilus influenzae in 7 (9%), Legionella pneumophila in 7 (9%), Streptococcus viridans in 3 (4%), Coxiella burnetii in 3 (4%), Mycoplasma pneumoniae in 2 (3%), Nocordia asteroides 2, Aspergillus ssp. 1, and others 10. In three of these cases the etiology was polymicrobial. Bacteremia was present in 19 (15%) cases; S. pneumoniae was the most frequent isolate (13 cases). Antibiotic treatment was modified in 22 cases due to etiologic findings, and in 9 due to therapeutic failure. Ten patients died (8%), and 22 needed mechanical ventilation, the mortality rate in the latter population being 23%. Total or partial resistance of S. pneumoniae to penicillin was observed in 10 of 32 (31%) isolations, and to erythromycin in 2 (6%). The results of this study are important for the standardization of empiric antibiotic strategies in COPD patients with pneumonia.
This study aimed to investigate the microbial aetiology of community-acquired pneumonia (CAP) in patients requiring hospitalization.
A prospective study of consecutive non-immunocompromised patients aged 12 years and above admitted with CAP from August 1997 to May 1999 was undertaken.
Of 127 patients hospitalized for CAP, an aetiological diagnosis was achieved in 53 cases (41.7%). Klebsiella pneumoniae was the most frequently isolated pathogen and caused 10.2% of all the cases, followed by Streptococcus pneumoniae (5.5%), Haemophilus influenzae (5.5%), Mycoplasma pneumoniae (3.9%) and Pseudomonas aeruginosa (3.9%). Gram-negative bacilli were significantly more frequently identified in patients aged 60 years or older and in patients with comorbid illnesses. Twelve of 13 patients who died from CAP had other comorbid illnesses compared to 63 of 114 patients who survived (P = 0.014). Three of eight bacteraemic patients died compared with 10 of 119 non-bacteraemic patients (P = 0.035).
The microbiology of CAP in patients requiring hospitalization in Malaysia appears to be different from that in Western countries. Gram-negative bacilli were more frequently isolated in older patients and in those with comorbidity. Mortality from CAP is more likely in patients with comorbidity and in those who are bacteraemic.
To describe and compare the background, clinical manifestations, disease course, and infectious etiologies of pneumonic acute exacerbations (PNAE) vs nonpneumonic acute exacerbations (NPAE) of COPD.
A prospective, observational study.
A tertiary university medical center in southern Israel.
Twenty-three hospitalizations for PNAE and 217 hospitalizations for NPAE were included in the study. Paired sera were obtained for each of the hospitalizations and were tested serologically for 12 pathogens. Only a significant change in antibody titers or levels was considered diagnostic.
No significant differences were found between the two groups for any of the parameters related to COPD or comorbidity. The clinical type of the exacerbation was not significantly different between the groups. Compared to NPAE, patients with PNAE had lower PO(2) values at hospital admission (p = 0.004) but higher rates of abrupt onset (p = 0.005), ICU admissions (p = 0.006), invasive mechanical ventilation (p = 0.01), mortality (p = 0.007), and longer hospital stay (p = 0.001). In 22 PNAE hospitalizations (96%) and in 153 NPAE hospitalizations (71%), at least one infectious etiology was identified (p = 0.001). Mixed infection was found in 13 patients with PNAE (59%) and in 59 patients with NPAE (39%; not significant [NS]). Viral etiology was identified in 18 patients with PNAE (78%) compared with 99 patients with NPAE (46%; p = 0.003). Pneumococcal etiology was found in 10 patients with PNAE (43%) and in 38 patients with NPAE (18%; p = 0.006). An atypical etiology was identified in 8 patients with PNAE (35%) and 64 patients with NPAE (30%; NS).
Community-acquired pneumonia is common among patients hospitalized for an acute exacerbation of COPD and is generally manifested by more severe clinical and laboratory parameters. In PNAE, compared to NPAE, viral and pneumococcal etiologies are more common, but the rate of atypical pathogens is similar. The therapeutic significance of these findings should be investigated further.
To investigate the frequency of respiratory bacterial infections in hospitalized patients, admitted with an acute exacerbation of chronic obstructive pulmonary disease (COPD), to identify the responsible pathogens by sputum culture and to assess patient characteristics in relation to sputum culture results.
We prospectively evaluated clinical data and sputum culture results of 171 patients, admitted to the pulmonology department of the University Hospital Maastricht with an acute exacerbation of COPD from 1st January 1999 until 31st December 1999.
Eighty-five patients (50%) had positive sputum cultures, indicating the presence of bacterial infection. Pathogens most frequently isolated were: Haemophilus influenzae (45%), Streptococcus pneumoniae (27%), and Pseudomonas aeruginosa (15%). Patients with more severely compromised lung function had a higher incidence of bacterial infections (P = 0.026). There were no significant differences in age, lung function parameters, blood gas results and length of hospital stay between patients with and without bacterial infection. There were no correlations between the type of bacteria isolated and clinical characteristics.
Incidence of bacterial infection during acute exacerbations of COPD is about 50%. Patients with and without bacterial infection are not different in clinical characteristics or in outcome parameters. Patients with lower FEV1 have a higher incidence of bacterial infections, but there is no difference in the type of bacterial infection. In the future, the pathogenic role of bacterial infection in exacerbations of COPD should be further investigated, especially the role of bacterial infection in relation to local and systemic inflammation.
Different inflammatory cell profiles are observed in the lungs of patients with asthma versus those with chronic obstructive pulmonary disease (COPD). In asthma, several key mediators have been implicated, including tumor necrosis factor-alpha and interleukin (IL)-1beta, together with cytokines derived from type 2 T-helper lymphocytes, such as IL-4, IL-5, and IL-13. In fact, inhibitors of IL-4 and IL-5 show promise as therapeutic agents. In COPD, the predominant inflammatory cell types are CD8(+) T lymphocytes, macrophages, and neutrophils. Glucocorticoids inhibit eosinophils in asthma, neutrophils in COPD and severe asthma, mast cells and basophils in asthma and COPD, and macrophages in COPD. However, it is generally assumed that neutrophils are less sensitive to glucocorticoids than are eosinophils and T cells, and that macrophages from patients with COPD are less sensitive to steroid treatment under certain circumstances. These differences in the responsiveness of activated inflammatory cells may help to explain why inhaled corticosteroid treatment has been more beneficial for patients with asthma than for patients with COPD.
To study the sputum microbiology of patients admitted to a teaching hospital with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with concomitant pneumonia.
This was a retrospective study in a tertiary university hospital in Hong Kong. All episodes of AECOPD with pneumonia, patient demographics, length of stay, sputum culture and radiological results admitted in the first half of the year 2000 were retrieved from hospital records.
There were 118 patients (91 male) with 150 episodes of AECOPD with concomitant pneumonia. The age of the patients was 74.8 +/- 10.0 years. Positive routine sputum culture was detected in 45.6% of the patients. Among these hospital admissions, 8.7, 4.0 and 12.0%, respectively, required intensive care unit admissions, mechanical ventilation and non-invasive positive pressure ventilation. Haemophilus influenzae was the commonest organism found in sputum (26.0%), followed by Pseudomonas aeruginosa (5.5%), Streptococcus pneumoniae (3.4%), and Moraxella catarrhalis (3.4%). Mycobacterium tuberculosis was found in 1.5% of the admissions. The presence of P. aeruginosa in sputum was associated with a longer hospital length of stay (9.1 +/- 3.1 vs. 7.1 +/- 4.2 days, P = 0.03).
In contrast to most other studies reporting S. pneumoniae as the most likely bacterial pathogen, H. influenzae was the commonest bacterium isolated in sputum in our patients with AECOPD and concomitant pneumonia.
The accuracy of reference values of lung function is important for assessment of severity and functional impairment of respiratory diseases. The aim of the study was to establish updated prediction formulae of spirometric parameters for Hong Kong Chinese and to compare the reference values with those derived from other studies in white and Chinese subjects.
Cross-sectional multicenter study.
Lung function laboratories of eight regional hospitals in Hong Kong.
Subjects were recruited by random-digit dialing. One thousand one hundred seventy-six subjects who fulfilled recruitment criteria underwent spirometry.
Spirometry was performed according to American Thoracic Society recommendations, and the technique was standardized among the eight participating lung function laboratories.
Evaluable data of 1,089 (494 men and 595 women) healthy nonsmokers aged 18 to 80 years were analyzed. Age and height were found to be the major determinants of FEV1 and FVC, with a linear decline of height-adjusted values with age in both sexes. Spirometric values of this population have increased compared to Chinese populations of similar sex, age, and height two decades ago. Reference values derived from white populations were higher than our values by 5 to 19%, and the degree of overestimation varied with age, sex, and lung function parameter. We also demonstrated that the blanket application of correction factors for Asian populations may not be appropriate. In this study cohort, the distribution-free estimation of age-related centiles was more appropriate for the determination of lower limits of normal.
Our findings underscore the need to use reference values based on updated data derived from local populations or those matched for ethnicity and other sociodemographic characteristics.
Infection is a major cause of acute exacerbations of COPD (AECOPDs). We aimed to study the infectious etiology related to AECOPD.
Patients admitted to an acute care hospital in Hong Kong with an AECOPD were recruited prospectively from May 1, 2004, to April 30, 2005. Sputum samples, nasopharyngeal aspirate (NPA) samples, and paired serology specimens were collected. Spirometry was performed with patients in the stable phase 2 to 3 months after hospital discharge.
There were 643 episodes of AECOPD among 373 patients. Their mean age was 75.3 years (SD, 7.9 years) with 307 male patients. The mean FEV(1) was 40.4% predicted (SD, 18.7% predicted), and the mean FEV(1)/FVC ratio was 58.4% (SD, 16.0%). Among sputum samples from the 530 episodes of AECOPD hospital admissions that were saved, 13.0%, 6.0%, and 5.5%, respectively, had positive growth of Haemophilus influenzae, Pseudomonas aeruginosa, and Streptococcus pneumoniae. Among the 505 hospital admissions with patients who had NPA samples saved, 5.7%, 2.3%, 0.8%, and 0.8%, respectively, had influenza A, respiratory syncytial virus (RSV), influenza B, and parainfluenza 3 isolated from viral cultures. Paired serology test results revealed a fourfold rise in viral titers in 5.2%, 2.2%, and 1.4% of patients, respectively, for influenza A, RSV, and influenza B. Very severe airflow obstruction (stable-state spirometry) was associated with a higher chance of a positive sputum culture (FEV(1) >/= 30% predicted, 28.2%; FEV(1) < 30% predicted, 40.4%; p = 0.006).
H influenzae and influenza A were the most common etiologic agents in patients who were hospitalized with AECOPDs. More severe airflow obstruction was associated with a higher chance of a positive sputum culture finding.
Nosocomial pneumonia is a common complication in mechanically ventilated patients. A study was carried out to determine the incidence, common bacterial etiologic agents and their antimicrobial susceptibility, and outcome of such pneumonia in an Intensive Care Unit (ICU) of a tertiary care center. In Surgical ICU (SICU) 176 patients required mechanical ventilation for more than 72 hours. A total of 39 (22.1%) of these patients developed nosocomial bacterial pneumonia as determined by microbiological assays. Endotracheal aspirate cultures detected a single bacterial isolate in 22 (56.4%) patients while two and three organisms were isolated from 10 (25.6%) and 7 (17.9%) patients respectively. Fifty three (84.1%) of a total of 63 isolates were Gram negative bacilli. The most frequently encountered pathogens were Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter species among the Gram negative bacilli and Staphylococcus aureus among the Gram positives. Resistance of bacterial isolates varied from 24 to 90% against commonly used antibiotics. Amikacin had the best profile, with 14% to 55% resistance against various isolates. Twenty three (59%) of 39 patients with pneumonia expired in the ICU. P. aeruginosa (25.6%) and K. pneunmoniae (17.9%) were the predominant isolates in these patients. Nosocomial pneumonia with high mortality is a frequent occurrence in mechanically ventilated patients in our ICU setting. Gram negative organisms with high levels of antimicrobial resistance are the most common isolates. Regular surveillance and monitoring of changes in antibiotic susceptibility of bacterial pathogens and appropriate therapeutic measures are likely to reduce the mortality in these patients.
Little information is available on the types, causes, and treatment of pneumonia in intensive care unit patients in usual clinical practice.
To characterize treatment of patients with presumed pneumonia in a tertiary care intensive care unit and to identify potential areas for improvement in care.
In a prospective, cohort study, the sample consisted of all consecutive patients treated in an intensive care unit during a 3-month period. For patients with presumed pneumonia, data were collected on incidence of pneumonia, diagnostic investigations, microbial isolates, and antibiotics prescribed.
Of 194 admissions, 73 patients were treated for pneumonia: 47 had community-acquired pneumonia; 12 had hospital-acquired pneumonia; 12 had ventilator-associated pneumonia, both early (7) and late (5); and 2 had intensive care unit-acquired pneumonia. Approximately 71% of patients had microbiological tests performed. Among 54 microbial isolates, 51.9% were gram-positive bacteria, 31.5% were gram-negative bacteria, and 9.3% were Candida species. The most commonly used antimicrobials were quinolones (54 of 192 prescriptions) and cephalosporins (33); each patient received a median of 3 antibiotics.
Most cases of pneumonia were community acquired. The most common causative organisms were gram-positive cocci. Four quality improvement strategies were rationalization of antibiotic use during rounds, nurses' reporting of culture results, review of antibiotic appropriateness by a pharmacist, and redesign of the clinical information system.
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- National Heart
- Blood Lung
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- B M Diederen
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- M F Peeters
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Diederen BM, van der Valk PD, Kluytmans JA, Peeters MF,
Hendrix R. The role of atypical respiratory pathogens in
Supplementary data
Supplementary data associated with this article can be
found in the online version, at doi:10.1016/j.rmed.
2008.03.019.
exacerbations of chronic obstructive pulmonary disease. Eur
Respir J 2007;30(2):240e4.
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Viral etiology of acute exacerbations of chronic obstructive pulmonary disease in Hong Kong
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