Phenotypic comparison between smoking and non-smoking chronic obstructive pulmonary disease.

BACKGROUND: Although COPD among non-smokers (NS-COPD) is common, little is known about this phenotype. We compared NS-COPD subjects with smoking COPD (S-COPD) patients in a rural Indian population using a variety of clinical, physiological, radiological, sputum cellular and blood biomarkers. METHODS: Two hundred ninety subjects (118 healthy, 79 S-COPD, 93 NS-COPD) performed pre- and post-bronchodilator spirometry and were followed for 2 years to study the annual rate of decline in lung function. Body plethysmography, impulse oscillometry, inspiratory-expiratory HRCT, induced sputum cellular profile and blood biomarkers were compared between 49 healthy, 45 S-COPD and 55 NS-COPD subjects using standardized methods. Spirometric response to oral corticosteroids was measured in 30 female NS-COPD patients. RESULTS: Compared to all male S-COPD subjects, 47% of NS-COPD subjects were female, were younger by 3.2 years, had greater body mass index, a slower rate of decline in lung function (80 vs 130 mL/year), more small airways obstruction measured by impulse oscillometry (p < 0.001), significantly less emphysema (29% vs 11%) on CT scans, lower values in lung diffusion parameters, significantly less neutrophils in induced sputum (p < 0.05) and tended to have more sputum eosinophils. Hemoglobin and red cell volume were higher and serum insulin lower in S-COPD compared to NS-COPD. Spirometric indices, symptoms and quality of life were similar between S-COPD and NS-COPD. There was no improvement in spirometry in NS-COPD patients after 2 weeks of an oral corticosteroid. CONCLUSIONS: Compared to S-COPD, NS-COPD is seen in younger subjects with equal male-female predominance, is predominantly a small-airway disease phenotype with less emphysema, preserved lung diffusion and a slower rate of decline in lung function.

Bacterial load and defective monocyte-derived macrophage bacterial phagocytosis in biomass smoke-related COPD.

Lower airway colonisation with species of potentially pathogenic bacteria (PPB) is associated with defective bacterial phagocytosis, in monocyte-derived macrophages (MDMs) and alveolar macrophages, from tobacco smoke-associated chronic obstructive pulmonary disease (S-COPD) subjects. In the developing world, COPD among nonsmokers is largely due to biomass smoke (BMS) exposure; however, little is known about PPB colonisation and its association with impaired innate immunity in these subjects.We investigated the PPB load (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Pseudomonas aeruginosa) in BMS-exposed COPD (BMS-COPD) subjects compared with S-COPD and spirometrically normal subjects. We also examined the association between PPB load and phagocytic activity of MDMs and lung function. Induced sputum and peripheral venous blood samples were collected from 18 healthy nonsmokers, 15 smokers without COPD, 16 BMS-exposed healthy subjects, 19 S-COPD subjects and 23 BMS-COPD subjects. PPB load in induced sputum and MDM phagocytic activity were determined using quantitative PCR and fluorimetry, respectively.Higher bacterial loads of S. pneumoniae, H. influenzae and P. aeruginosa were observed in BMS-COPD subjects. Increased PPB load in BMS-exposed subjects was significantly negatively associated with defective phagocytosis in MDMs and spirometric lung function indices (p<0.05).Increased PPB load in airways of BMS-COPD subjects is inversely associated with defective bacterial phagocytosis and lung function.

Evaluating the role of leukotriene-modifying drugs in asthma management: Are their benefits 'losing in translation'?

Leukotrienes (LTs) initiate a cascade of reactions that cause bronchoconstriction and inflammation in asthma. LT-modifying drugs have been proved very effective to reduce inflammation and associated exacerbation however despite some illustrious clinical trials the usage of these drugs remains overlooked because the evidence to support their utility in asthma management has been mixed and varied between studies. Although, there are plenty of evidences which suggest that the leukotriene-modifying drugs provide consistent improvement even after just the first oral dose and reduce asthma exacerbations, the beneficial effect of these drugs has remained sparse and widely debated. And these beneficial effects are often overlooked because most of the clinical studies include a mixed population of asthmatics who do not respond to LT-modifiers equally. Therefore, in the present era of personalized medicine, it is important to properly stratify the patients and non-invasive measurements of biomarkers may warrant the possibility to characterize biological/pathological pathway to direct treatment to those who will benefit from it. Endotyping based on individual's leukotriene levels should probably ascertain a subgroup of patients that would clearly benefit from the treatment even though the trial fails to show overall significance. In this article, we have methodically evaluated contemporary literature describing the efficacy of LT-modifying drugs in the management of asthma and highlighted the importance of phenotyping the asthmatics for better treatment outcomes.