Association of chronic obstructive pulmonary disease severity and Pneumocystis colonization.

M.S., Division of Pulmonary and Critical Care Medicine, 2011 Zonal Avenue, Los Angeles, CA 90033, USA.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 11.99). 09/2004; 170(4):408-13. DOI: 10.1164/rccm.200401-094OC
Source: PubMed

ABSTRACT Factors modulating the variable progression of chronic obstructive pulmonary disease (COPD) are largely unknown, but infectious agents may play a role. Because Pneumocystis has previously been shown to induce a CD8(+) lymphocyte- and neutrophil-predominant response similar to that in COPD, we explored the association of the organism with accelerated disease progression. We examined Pneumocystis colonization rates in lung tissue obtained during lung resection or transplantation in smokers with a range of airway obstruction severity and in a control group with lung diseases other than COPD. Using nested polymerase chain reaction, Pneumocystis colonization was detected in 36.7% of patients with very severe COPD (Global Health Initiative on Obstructive Lung Disease [GOLD] Stage IV) compared with 5.3% of smokers with normal lung function or less severe COPD (Stages 0, I, II, and III) (p = 0.004) and with 9.1% of control subjects (p = 0.007). Colonized subjects exhibited more severe airway obstruction (median FEV(1) = 21% predicted versus 62% in noncolonized subjects, p = 0.006). GOLD IV was the strongest predictor of Pneumocystis colonization (odds ratio = 7.3, 95% confidence interval = 2.4-22.4, p < 0.001) and was independent of smoking history. We conclude that there is a strong association between Pneumocystis colonization and severity of airflow obstruction in smokers, suggesting a possible pathogenic link with COPD progression.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the context of deciphering the metabolic strategies of the obligate pathogenic fungi in the genus Pneumocystis, the genomes of three species (P. carinii, P. murina, and P. jirovecii) were compared among themselves and with the free-living, phylogenetically related fission yeast (Schizosaccharomyces pombe). The underrepresentation of amino acid metabolism pathways compared to those in S. pombe, as well as the incomplete steroid biosynthesis pathway, were confirmed for P. carinii and P. jirovecii and extended to P. murina. All three Pneumocystis species showed overrepresentation of the inositol phosphate metabolism pathway compared to that in the fission yeast. In addition to those known in S. pombe, four genes, encoding inositol-polyphosphate multikinase (EC, inositol-pentakisphosphate 2-kinase (EC, phosphoinositide 5-phosphatase (EC, and inositol-1,4-bisphosphate 1-phosphatase (EC, were identified in the two rodent Pneumocystis genomes, P. carinii and P. murina. The P. jirovecii genome appeared to contain three of these genes but lacked phosphoinositide 5-phosphatase. Notably, two genes encoding enzymes essential for myo-inositol synthesis, inositol-1-phosphate synthase (INO1) and inositol monophosphatase (INM1), were absent from all three genomes, suggesting that Pneumocystis species are inositol auxotrophs. In keeping with the need to acquire exogenous inositol, two genes with products homologous to fungal inositol transporters, ITR1 and ITR2, were identified in P. carinii and P. murina, while P. jirovecii contained only the ITR1 homolog. The ITR and inositol metabolism genes in P. murina and P. carinii were expressed during fulminant infection as determined by reverse transcriptase real-time PCR of cDNA from infected lung tissue. Supplementation of in vitro culture with inositol yielded significant improvement of the viability of P. carinii for days 7 through 14.
    mBio 10/2014; 5(6). · 6.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have suggested that human immunodeficiency virus (HIV) infection and/or the airway colonization of Pneumocystis jirovecii (Pcj) impact on the progression of airway obstruction, such as chronic obstructive pulmonary disease (COPD). This study was aimed to evaluate the relationship between HIV infection, airway colonization of Pcj and airway obstruction in Japanese male patients. Case-control study of 49 HIV-positive and 257 HIV-negative men were enrolled in this study. Airway obstruction was determined by spirometry. Cigarette smoking was determined by a self report. Laboratory data were obtained from medical records. Among HIV positive patients, the airway colonization of Pcj was evaluated by induced sputum using the real time polymerase chain reaction method. Forty-eight out of 49 (97.9%) HIV-positive patients received antiretroviral therapy, and their median CD4 cell counts were 491/μL (79-935). The prevalence of airway obstruction as determined by spirometry was 10.2% (5/49) in HIV-positive subjects and 2.4% (5/208) in HIV-negative subjects (p = 0.024). Compared with the control group, HIV-positive patients were significantly younger (median age 44 vs 40, p = 0.019). After adjusting for age, pack-years of smoking, HIV infection was an independent risk factor for airway obstruction (OR; 10.93, 95%CI 1.99-60.1, p = 0.006). None of patient was detected the airway colonization of Pcj. HIV infection was an independent risk factor for airway obstruction regardless of airway colonization of Pcj. Health-care providers should be aware of the increased likelihood of airway obstruction among HIV-positive patients.
    Journal of Infection and Chemotherapy 03/2014; · 1.38 Impact Factor
  • Rheumatology 11/2012; 51(12):2120-2130. · 4.44 Impact Factor

Full-text (2 Sources)

Available from
Jul 3, 2014