Parameswaran Nair

Publications of Parameswaran Nair

• Equivalence Considerations for Orally Inhaled Products for Local Action-ISAM/IPAC-RS European Workshop Report.

  Authors: Carole Evans, David Cipolla, Tim Chesworth, Eva Agurell, Richard Ahrens, Dale Conner, Sanjeeva Dissanayake, Myrna Dolovich, William Doub, Anders Fuglsang [......] Svetlana Lyapustina, Parameswaran Nair, Dennis O'Connor, David Parkins, Ilse Peterson, Colin Reisner, Dennis Sandell, Gur Jai Pal Singh, Marjolein Weda, Patricia Watson

  Journal of aerosol medicine and pulmonary drug delivery. 03/2012;

  Abstract The purpose of this article is to document the discussions at the 2010 European Workshop on Equivalence Determinations for Orally Inhaled Drugs for Local Action, cohosted by theAbstract The purpose of this article is to document the discussions at the 2010 European Workshop on Equivalence Determinations for Orally Inhaled Drugs for Local Action, cohosted by the International Society for Aerosols in Medicine (ISAM) and the International Pharmaceutical Consortium on Regulation and Science (IPAC-RS). The article summarizes current regulatory approaches in Europe, the United States, and Canada, and presents points of consensus as well as ongoing debate in the four major areas: in vitro testing, pharmacokinetic and pharmacodynamic studies, and device similarity. Specific issues in need of further research and discussion are also identified.

• Proximity to major roadways is a risk factor for airway hyper-responsiveness in adults.

  Authors: Shannon Riley, Julie Wallace, Parameswaran Nair

  Canadian respiratory journal : journal of the Canadian Thoracic Society. 03/2012; 19(2):89-95.

  Proximity to major roads is reported to be associated with asthma and airway hyper-responsiveness in children. Similar studies using objective measurements in adults are not available in Canada. ToProximity to major roads is reported to be associated with asthma and airway hyper-responsiveness in children. Similar studies using objective measurements in adults are not available in Canada. To test the hypothesis that adult asthmatic patients who live close to major roads and highways in an urban environment are at a risk of moderate to severe airway hyper-responsiveness. Airway responsiveness was determined using methacholine bronchial provocation (PC 20<⁄span>) tests in a cohort of 2625 patients who attended an outpatient clinic in Hamilton, Ontario. Patient addresses were geocoded in a geographic information system to determine proximity to major roads and highways. Multivariate linear and multinomial regression analyses were used to assess whether proximity to roads was a risk factor for airway hyper-responsiveness as measured by PC 20<⁄span> methacholine. Patients who lived within 200 m of a major road had increased odds (OR 1.38 [95% CI 1.04 to 1.85]) of having moderate airway hyperresponsiveness (0.25 mg⁄mL <pc20 response=" normal=" a=" having=" with=" compared=" mg=" <2.0=" ml)=" (pc20=" ⁄>16 mg⁄mL). Spatial analysis also revealed that the majority of patients with severe airway hyper-responsiveness lived within the urban core of the city while those with moderate to mild hyper-responsiveness were also dispersed in rural areas. In an adult population of patients attending an outpatient respiratory clinic in Hamilton, living close to major roadways was associated with an increased risk of moderate airway hyper-responsiveness. This correlation suggests that exposure to traffic emissions may provoke the pathology of airway hyper-responsiveness leading to variable airflow obstruction.

• Cystic fibrosis transmembrane conductance regulator gene abnormalities in patients with asthma and recurrent neutrophilic bronchitis.

  Authors: Jodi Goodwin, Naomi Spitale, Asma Yaghi, Myrna Dolovich, Parameswaran Nair

  Canadian respiratory journal : journal of the Canadian Thoracic Society. 01/2012; 19(1):46-8.

  The present case series describes four patients with asthma, airway hyperresponsiveness and neutrophilic bronchitis who harboured abnormal cystic fibrosis transmembrance conductance regulator (CFTR)The present case series describes four patients with asthma, airway hyperresponsiveness and neutrophilic bronchitis who harboured abnormal cystic fibrosis transmembrance conductance regulator (CFTR) gene mutations. It serves both to alert clinicians to consider CFTR-related disease in both young and elderly patients with persistent neutrophilic bronchitis, and to highlight the potential utility of future genetic testing for CFTR abnormalities in patients with asthma and recurrent bronchitis or pansinusitis, and the role of nebulized hypertonic saline as a therapeutic option in these patients.

• In memoriam: Frederick E Hargreave (1938-2011).

  Authors: Paul M O'Byrne, Parameswaran Nair, Peter J Sterk

  Thorax. 12/2011; 66(12):1101-2.

• Serum procalcitonin and infective exacerbations of asthma.

  Authors: Liesel D'silva, Nesreen Hassan, Parameswaran Nair

  Chest. 11/2011; 140(5):1389-90; author reply 1390-1.

• Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study.

  Authors: Mario Castro, Sameer Mathur, Frederick Hargreave, Louis-Philippe Boulet, Fang Xie, James Young, H Jeffrey Wilkins, Timothy Henkel, Parameswaran Nair

  American journal of respiratory and critical care medicine. 08/2011; 184(10):1125-32.

  Eosinophilic asthma is a phenotype of asthma characterized by the persistence of eosinophils in the airways. IL-5 is involved in the activation and survival of eosinophils. To evaluate the effect ofEosinophilic asthma is a phenotype of asthma characterized by the persistence of eosinophils in the airways. IL-5 is involved in the activation and survival of eosinophils. To evaluate the effect of the antibody to IL-5, reslizumab, in patients with eosinophilic asthma that is poorly controlled with high-dose inhaled corticosteroid. Patients were randomly assigned to receive infusions of reslizumab at 3.0 mg/kg (n = 53) or placebo (n = 53) at baseline and at Weeks 4, 8, and 12, with stratification by baseline Asthma Control Questionnaire (ACQ) score less than or equal to 2 or greater than 2. The primary efficacy measure was the difference between the reslizumab and placebo groups in the change in ACQ score from baseline to end of therapy (Week 15 or early withdrawal). Mean changes from baseline to end of therapy in ACQ score were -0.7 in the reslizumab group and -0.3 in the placebo group (P = 0.054) and in FEV(1) were 0.18 and -0.08 L, respectively (P = 0.002). In those patients with nasal polyps, the changes in ACQ score were -1.0 and -0.1, respectively (P = 0.012). Median percentage reductions from baseline in sputum eosinophils were 95.4 and 38.7%, respectively (P = 0.007). Eight percent of patients in the reslizumab group and 19% of patients in the placebo group had an asthma exacerbation (P = 0.083). The most common adverse events with reslizumab were nasopharyngitis, fatigue, and pharyngolaryngeal pain. Patients receiving reslizumab showed significantly greater reductions in sputum eosinophils, improvements in airway function, and a trend toward greater asthma control than those receiving placebo. Reslizumab was generally well tolerated.

• Lipid and smoker's inclusions in sputum macrophages in patients with airway diseases.

  Authors: Andrew M Wilson, Parameswaran Nair, Frederick E Hargreave, Ann E Efthimiadis, Mehran Anvari, Christopher J Allen

  Respiratory medicine. 08/2011; 105(11):1691-5.

  We studied the effect of tobacco smoking on macrophage lipid index and macrophage smokers inclusions in induced sputum in 256 patients (143 non-smokers, 81 ex-smokers and 32 current smokers). LipidWe studied the effect of tobacco smoking on macrophage lipid index and macrophage smokers inclusions in induced sputum in 256 patients (143 non-smokers, 81 ex-smokers and 32 current smokers). Lipid index was, using the Oil red O stain, the sum of the lipid staining droplet score (range 0-4) in 100 macrophages. Smokers inclusions were assessed using Wright's stain and graded as "none", "few", "moderate" or "many". Lipid index was significantly higher in current smokers (112.5, SD 58.5 units) than ex-smokers (29.2, SD 42.8 units) or non-smokers (13.4, SD 121.7). Smokers inclusions were present in all current smokers but only in 2 non-smokers. The mean smoking history of current smokers with few macrophage inclusions was 15.0 (SD 11.2), moderate 21.6 (SD 15.7), and many 30.0 (SD 21.9) pack years. There was a significant difference between the length of time ex-smokers had quit smoking if they had no or few smokers inclusions (mean 17.6 (SD 11.2) years) compared to those with moderate or many smokers inclusions (mean 2.8 (SD 5.8) years) (p = 0.01). Lipid index was significantly correlated with smokers inclusions (r = 0.72, p < 0.01). We conclude that smoker's inclusions within sputum macrophages is a reliable indicator of cigarette smoking and that the sputum lipid index cannot be used as an assessment of oropharyngeal reflux in cigarette smokers.

• Persistent sputum cellularity and neutrophils may predict bronchiectasis.

  Authors: Nicole Drost, Liesel D'silva, Ryan Rebello, Ann Efthimiadis, Frederick E Hargreave, Parameswaran Nair

  Canadian respiratory journal : journal of the Canadian Thoracic Society. 07/2011; 18(4):221-4.

  Quantitative cell counts in sputum provide an accurate assessment of the type and severity of bronchitis. To examine whether sputum cell counts could identify bronchiectasis in patients withQuantitative cell counts in sputum provide an accurate assessment of the type and severity of bronchitis. To examine whether sputum cell counts could identify bronchiectasis in patients with recurrent bronchitis. A retrospective survey of a clinical database (January 2004 to January 2005) of quantitative cell counts from sputum selected from expectorate in patients with obstructive airways diseases was used to identify predictors of bronchiectasis using ROC curves. This was prospectively evaluated (February 2005 to April 2008) using high-resolution computed tomography scans of thorax that were independently scored by a radiologist who was blinded to the clinical details. The retrospective survey identified 41 patients with bronchiectasis among 490 patients with airway diseases. Total cell count of 60×106⁄g or greater of the selected sputum with predominant neutrophils on two occasions had a sensitivity of 86.7%, a specificity of 87.5%, and positive and negative predictive values of 93% and 78%, respectively, to identify bronchiectasis. In the prospective study, 10 of 14 (71%) patients who met these criteria were identified to have bronchiectasis. Both total cell count and the percentage of neutrophils correlated with radiographic bronchiectasis severity. Persistent or recurrent intense sputum cellularity with neutrophilia is suggestive of bronchiectasis.

• Point: Is measuring sputum eosinophils useful in the management of severe asthma? Yes.

  Authors: Frederick E Hargreave, Parameswaran Nair

  Chest. 06/2011; 139(6):1270-3.

• Expiratory flows and airway inflammation in elderly asthmatic patients.

  Authors: Marie-Eve Ducharme, Philippe Prince, Nesreen Hassan, Parameswaran Nair, Louis-Philippe Boulet

  Respiratory medicine. 05/2011; 105(9):1284-9.

  Asthma in the elderly is often underrecognized and suboptimally treated, resulting in an increased morbidity and mortality. The characteristics of asthma-related bronchitis and its optimal treatmentAsthma in the elderly is often underrecognized and suboptimally treated, resulting in an increased morbidity and mortality. The characteristics of asthma-related bronchitis and its optimal treatment remain to be determined in this population. We aimed to compare lung function and airway inflammation in elderly and younger asthmatic subjects. Data from two induced sputum databases were analyzed in three groups of asthmatic subjects (18-30 y, n = 136; 31-59 y, n = 385; 60-72 y, n = 172) and one group of healthy elderly subjects (60-89 y, n = 16). Expiratory flows and induced sputum cell counts were analyzed. Airway obstruction was more marked in elderly asthmatics compared with healthy elderly or younger asthmatic subjects (p < 0.01). An increase in sputum neutrophils and a decrease in macrophages and lymphocytes were observed in elderly asthmatics (p < 0.0001). Neutrophil percentages significantly increased with asthma severity in the young and the middle-aged groups, while they remained similar in elderly asthmatics regardless of asthma severity (p < 0.05). Neutrophil percentages weakly correlated with the dose of ICS in all asthmatics (r = 0.17, p < 0.0001). Age and dose of ICS were independent predictors of neutrophil percentage in asthmatic subjects in a regression model (R(2) = 0.12). Asthma in the elderly is associated with a more marked airway obstruction and sputum neutrophilia. Both age and the dose of corticosteroids need to be considered in the interpretation of the clinical relevance of sputum neutrophil count.

• Nontubercular mycobacterial pulmonary infection in severe asthma.

  Authors: Parameswaran Nair

  Chest. 03/2011; 139(3):721; author reply 721-2.

• Early interventions with inhaled corticosteroids in asthma: benefits and risks.

  Authors: Parameswaran Nair

  Current opinion in pulmonary medicine. 01/2011; 17(1):12-5.

  the present review examines the effects of early intervention with inhaled corticosteroids (ICSs) on clinical efficacy and natural history of asthma based on two recent clinical trials: the Inhaledthe present review examines the effects of early intervention with inhaled corticosteroids (ICSs) on clinical efficacy and natural history of asthma based on two recent clinical trials: the Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) and Prevention of Early Asthma in Kids (PEAK) trials, and a comparison of the effect of regular vs. intermittent therapy based on the Improving Asthma Control Trial (IMPACT). in most patients, both adults and children, who have a new diagnosis of asthma and whose symptoms are mild but persistent, treatment with ICS should be recommended as soon as the diagnosis is made. This is a cost-effective and well tolerated treatment. However, symptoms may recur and lung function may decline again if treatment is discontinued. ICS is the most cost-effective initial treatment for both adults and children with a new diagnosis of asthma. If patients are reluctant to use ICS daily for long periods, it would be reasonable to delay the onset of treatment with ICS. Initial therapy with leukotriene receptor antagonist is not likely to be as effective as initial therapy with ICS. Biomarkers of airway inflammation such as sputum cell counts and exhaled nitric oxide are probably not necessary to treat patients with mild intermittent asthma.

• Reply.

  Authors: Parameswaran Nair, Paul M O'Byrne, Frederick E Hargreave

  The Journal of allergy and clinical immunology. 12/2010;

• Paranasal sinus disease and sputum eosinophilia in prednisone-dependent asthma.

  Authors: Bosco T M Lui, Colm Boylan, Afia Aziz-Ur-Rehman, Doron D Sommer, Parameswaran Nair

  Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale. 12/2010; 39(6):703-9.

  to investigate the extent and characteristics of paranasal sinus abnormalities (anatomic and mucosal) on computed tomographic (CT) sinus scans and to determine whether there is a relationship betweento investigate the extent and characteristics of paranasal sinus abnormalities (anatomic and mucosal) on computed tomographic (CT) sinus scans and to determine whether there is a relationship between these findings and eosinophilic airway inflammation in patients with prednisone-dependent asthma. we conducted an observational survey of 15 prednisone-dependent asthmatic patients with respect to measures of airway inflammation and CT sinus scans. The pathologic changes on the CT scans were scored using the Lund-Mackay and JAMA staging systems, and several paranasal bony anatomic variations were recorded. Correlations between CT sinus measures and sputum eosinophil count as well as prednisone dose requirement to control sputum eosinophilia were examined. the JAMA and Lund-Mackay staging systems showed that greater sphenoidal mucosal disease was associated with increased prednisone dose requirements (OR 1.7, p = .05; OR 1.6, p = .021). Generally, both staging systems showed that specific sinus site involvement correlated with higher levels of sputum eosinophils. Mucosal thickening in the sphenoid sinus correlated most closely with sputum eosinophilia, followed by the maxillary and ethmoid sinuses and osteomeatal complex. Finally, there appeared to be a limited role for sinus anatomy as a predictive factor for the dose of prednisone required to control sputum eosinophilia. sinomucosal thickening, but not sinus anatomy, appears to be an important predictor of prednisone requirement and severity of eosinophilic bronchitis in severe asthma.

• Measuring bronchitis in airway diseases: clinical implementation and application: Airway hyperresponsiveness in asthma: its measurement and clinical significance.

  Authors: Parameswaran Nair, Frederick E Hargreave

  Chest. 08/2010; 138(2 Suppl):38S-43S.

  Airway inflammation is fundamental to the cause and persistence of asthma and other airway conditions. It contributes to symptoms, variable airflow limitation, airway hyperresponsiveness, and theAirway inflammation is fundamental to the cause and persistence of asthma and other airway conditions. It contributes to symptoms, variable airflow limitation, airway hyperresponsiveness, and the structural changes (remodeling) associated with asthma. However, the presence and type of airway inflammation can be difficult to detect clinically, delaying the introduction of appropriate treatment. Cellular inflammation in the airway can be accurately and reliably assessed by examining spontaneous or, when not available, induced sputum. Induced sputum cell counts are relatively noninvasive, safe, and reliable. They can accurately discriminate eosinophilic airway inflammation from noneosinophilic airway inflammation and, thus, help to guide therapy. Eosinophilic airway inflammation is steroid responsive, whereas noneosinophilic (usually neutrophilic) inflammation generally is not. Monitoring of airway inflammation using sputum cell counts helps to identify the impending loss of asthma control and, thus, the need to adjust antiinflammatory medications in patients with a variety of airway diseases, such as asthma, smoker's COPD, and chronic cough. Other noninvasive, indirect measurements of airway inflammation, such as exhaled nitric oxide, do not help to identify the cellular nature of airway inflammation associated with exacerbations of airway diseases, particularly in patients who are already on corticosteroids. Thus, although they can be a predictor of steroid responsiveness, these measures do not help to reduce asthma exacerbations when used in clinical practice. The clinical usefulness of measurements in exhaled breath condensate has not yet been established.

• Nitric oxide in exhaled breath is poorly correlated to sputum eosinophils in patients with prednisone-dependent asthma.

  Authors: Parameswaran Nair, Melanie Kjarsgaard, Susan Armstrong, Ann Efthimiadis, Paul M O'Byrne, Frederick E Hargreave

  The Journal of allergy and clinical immunology. 08/2010; 126(2):404-6.

• Atmospheric remote sensing to detect effects of temperature inversions on sputum cell counts in airway diseases.

  Authors: Julie Wallace, Parameswaran Nair, Pavlos Kanaroglou

  Environmental research. 08/2010; 110(6):624-32.

  Temperature inversions result in the accumulation of air pollution, often to levels exceeding air quality criteria. The respiratory response may be detectable in sputum cell counts. This studyTemperature inversions result in the accumulation of air pollution, often to levels exceeding air quality criteria. The respiratory response may be detectable in sputum cell counts. This study investigates the effect of boundary layer temperature inversions on sputum cell counts. Total and differential cell counts of neutrophils, eosinophils, macrophages and lymphocytes were quantified in sputum samples of patients attending an outpatient clinic. Temperature inversions were identified using data from the Atmospheric Infrared Sounder, an atmospheric sensor on the Aqua spacecraft which was launched in 2002 by the National Aeronautics and Space Administration. On inversion days, a statistically significant increase in the percent of cells that were neutrophils was observed in stable patients. There was also a statistically significant increase in the percent of cells that were macrophages, in exacerbated patients. Multivariate linear regression models were used to assess the relationship between temperature inversions and cell counts, controlling patients' age, smoking status, medications and meteorological variables of temperature and humidity. The analyses indicate that, in the stable and exacerbated groups, percent neutrophils and macrophages increased by 12.6% and 2.5%, respectively, on inversion days. These results suggest that temperature inversions need consideration as an exacerbating factor in bronchitis and obstructive airway disease. The effects of air pollutants, nitrogen dioxide, carbon monoxide, fine particulate matter and ozone, were investigated. We identified no significant associations with any pollutant. However, we found that monthly averages of total cell counts were strongly correlated with monthly nitrogen dioxide concentrations, an association not previously identified in the literature.

• Airway responsiveness to indirect challenges in COPD.

  Authors: Nesreen M Hassan, Frederick E Hargreave, Parameswaran Nair

  COPD. 04/2010; 7(2):133-40.

  Patients with chronic obstructive pulmonary disease (COPD) demonstrate airway hyperresponsiveness to a number of indirect stimuli. Hyperresponsiveness to cold air hyperventilation, exercise, andPatients with chronic obstructive pulmonary disease (COPD) demonstrate airway hyperresponsiveness to a number of indirect stimuli. Hyperresponsiveness to cold air hyperventilation, exercise, and drugs like propranalol and methoxamine seem to be able to distinguish patients with COPD from those with asthma, whereas hyperresponsiveness to stimuli like adenosine 5-monophosphate (AMP) and hypertonic saline seem unable to do so. The relationship of airway responsiveness to indirect stimuli and airway inflammation has received little study. The clinical relevance of hyperresponsiveness to an indirect challenge, including the impact on the natural history, relation to types of bronchitis, baseline airway calibre, and response to treatment need to be studied.

• Human cellular response to temperature inversions detected by the Atmospheric Infrared Sounder (AIRS).

  Authors: Julie Wallace, Parameswaran Nair, Pavlos S. Kanaroglou

  IEEE International Geoscience & Remote Sensing Symposium, IGARSS 2010, July 25-30, 2010, Honolulu, Hawaii, USA, Proceedings; 01/2010

• Clinical equivalence testing of inhaled bronchodilators.

  Authors: Parameswaran Nair, John Hanrahan, Frederick Hargreave

  Polskie archiwum medycyny wewnetrznej. 11/2009; 119(11):731-735.

  There are no standardized methods to demonstrate in-vivo bioequivalence of inhaled bronchodilators. The most practical method of showing therapeutic equivalence in vivo is by estimating theirThere are no standardized methods to demonstrate in-vivo bioequivalence of inhaled bronchodilators. The most practical method of showing therapeutic equivalence in vivo is by estimating their relative potencies (RP) in clinical efficacy studies. The RP of bronchodilators may be estimated by comparing either their bronchodilator or bronchoprotective properties. Bronchodilator studies are easier to perform and may better model the physiologic effect of many agents, including inhaled beta-agonists. However, it may be difficult to demonstrate steep dose-response for these outcomes, except in cumulative study designs. Bioequivalence trials may be especially challenging when involving pressurized metered-dose inhalers, as a single actuation - the lowest feasible dose to include in the evaluation, may already produce bronchodilation that is at or near the plateau of the dose-response curve. Protection against bronchoconstriction induced by a direct inhaled stimulus like methacholine or histamine affords a reliable and practical method of comparing inhaled bronchodilators and estimating their RP. Inhalational bronchoprovocation testing allows for easier repeatability and quantitation of the stimulus necessary to produce a predetermined degree of bronchoconstriction, and the degree of protection afforded by the bronchoprotection agent. RP studies using adequate methodology are necessary to compare long-acting bronchodilators and both short- and long-acting bronchodilators in patients who are also on inhaled corticosteroids.