COPD and multimorbidity: recognising and addressing a syndemic occurrence.

Most patients with chronic obstructive pulmonary disease (COPD) have at least one additional, clinically relevant chronic disease. Those with the most severe airflow obstruction will die from respiratory failure, but most patients with COPD die from non-respiratory disorders, particularly cardiovascular diseases and cancer. As many chronic diseases have shared risk factors (eg, ageing, smoking, pollution, inactivity, and poverty), we argue that a shift from the current paradigm in which COPD is considered as a single disease with comorbidities, to one in which COPD is considered as part of a multimorbid state-with co-occurring diseases potentially sharing pathobiological mechanisms-is needed to advance disease prevention, diagnosis, and management. The term syndemics is used to describe the co-occurrence of diseases with shared mechanisms and risk factors, a novel concept that we propose helps to explain the clustering of certain morbidities in patients diagnosed with COPD. A syndemics approach to understanding COPD could have important clinical implications, in which the complex disease presentations in these patients are addressed through proactive diagnosis, assessment of severity, and integrated management of the COPD multimorbid state, with a patient-centred rather than a single-disease approach.

Chronic obstructive pulmonary disease in never-smokers: risk factors, pathogenesis, and implications for prevention and treatment.

Chronic obstructive pulmonary disease (COPD) was traditionally thought to be caused by tobacco smoking. However, recognition of the importance of non-smoking-related risk factors for COPD has increased over the past decade, with evidence on the burden, risk factors, and clinical presentations of COPD in never-smokers. About half of all COPD cases worldwide are due to non-tobacco-related risk factors, which vary by geographical region. These factors include air pollution, occupational exposures, poorly controlled asthma, environmental tobacco smoke, infectious diseases, and low socioeconomic status. Impaired lung growth during childhood, caused by a range of early-life exposures, is associated with an increased risk of COPD. Potential mechanisms for the pathogenesis of COPD in never-smokers include inflammation, oxidative stress, airway remodelling, and accelerated lung ageing. Compared with smokers who develop COPD, never-smokers with COPD have relatively mild chronic respiratory symptoms, little or no emphysema, milder airflow limitation, and fewer comorbidities; however, exacerbations can still be frequent. Further research-including epidemiological, translational, clinical, and implementation studies-is needed to address gaps in understanding and to advance potential solutions to reduce the burden of COPD in never-smokers.

Potential for integrating yoga within pulmonary rehabilitation and recommendations of reporting framework.

There is a rising burden of chronic obstructive pulmonary disease (COPD) in India. Pulmonary rehabilitation (PR), is a universally recommended multidisciplinary therapeutic strategy for the management of COPD; however, its needs are unmet. The diversity in the healthcare systems, availability of PR specialists and sociocultural multiformity requires contextualised and innovative PR models. Culturally sensitive elements, such as yoga, have some evidence of a positive impact in the management of COPD. Yoga and PR are based on similar principles with a holistic approach of involving physical activities, behaviour change techniques and psychological support to improve disease outcomes. Arguably the principles of PR and yoga are complementary but there are some important differences in the intensities of activities, exercise types and inclusion of mindfulness in components that must be considered. Components of PR enable aerobic capacity building, strengthening of muscles of the upper and lower extremities and building awareness towards disease management. Yoga, on the other hand, primarily can focus on core strengthening, breathing control, mindfulness and self-awareness. We discuss the potential of integrating the sociocultural appeal of yoga with PR delivered at international standards, and how an integrated approach may lead to optimal referral, uptake and completion.

Disruptions in oral and nasal microbiota in biomass and tobacco smoke associated chronic obstructive pulmonary disease.

Chronic exposures to tobacco and biomass smoke are the most prevalent risk factors for COPD development. Although microbial diversity in tobacco smoke-associated COPD (TSCOPD) has been investigated, microbiota in biomass smoke-associated COPD (BMSCOPD) is still unexplored. We aimed to compare the nasal and oral microbiota between healthy, TSCOPD, and BMSCOPD subjects from a rural population in India. Nasal swabs and oral washings were collected from healthy (n = 10), TSCOPD (n = 11), and BMSCOPD (n = 10) subjects. The downstream analysis was performed using QIIME pipeline (v1.9). In nasal and oral microbiota no overall differences were noted, but there were key taxa that had differential abundance in either Healthy vs COPD and/or TSCOPD vs. BMSCOPD. Genera such as Actinomyces, Actinobacillus, Megasphaera, Selenomonas, and Corynebacterium were significantly higher in COPD subjects. This study suggests that microbial community undergoes dysbiosis which may further contribute to the progression of disease. Thus, it is important to identify etiological agents for such a polymicrobial alterations which contribute highly to the disease manifestation.

A Cross-Sectional Survey of Practice Patterns and Selected Demographics of Respiratory Therapists in India.

BACKGROUND: Respiratory therapy was introduced to India in 1995. Respiratory therapists (RTs) work alongside doctors in hospitals. Of the 993 universities in India, a few have bachelor's or master's programs in respiratory therapy, but no studies have examined the demographics, geographical spread, or skills used by these RTs. This study assessed the demographics and services offered by RTs in India. METHODS: This was a cross-sectional study based on a survey administered on paper, by telephone, or online. RTs were selected by convenience sampling from institutional databases and from WhatsApp groups of RTs in India, as well through snowball sampling of co-workers. A link to the online survey was shared on the author's personal social media channels. Of the invited RTs, 465 consented and participated; of those, 237 answered all questions. RESULTS: Of the 237 respondents completing the survey, 73% had bachelor's degree, 16.5% had a master's degree, 4.6% had a diploma, 2.5% had mixed qualifications, 1.7% had post graduate diploma, 0.8% had a certificate, 0.4% had a master of business administration degree, and 0.4% had a PhD degree. Almost all (96.6%) worked as an RT or in a job that required respiratory therapy knowledge. Although individuals may have had multiple job roles, 77.6% worked as a hospital staff RT. The least frequently performed competencies were recommending diagnostic procedures, using evidence-based principles, initiating and conducting patient and family education, and administering home care and pulmonary rehabilitation; the most frequently performed competencies were support oxygenation and ventilation, ensuring infection control, and maintaining a patent airway. CONCLUSIONS: Most subjects were employed in south India and had a bachelor's degree. They worked as staff RTs with a focus on the acute care environment. Pneumonia, asthma, COPD, and ARDS were the most commonly managed diseases. Competencies such as recommending procedures, planning and providing pulmonary rehabilitation, and administering home-based care were the least frequently performed.

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.

Role of blood glucose and fat profile in lung function pattern of Indian type 2 diabetic subjects.

BACKGROUND AND OBJECTIVES: It has been hypothesized that changes in lung function can occur in patients with diabetes. Nevertheless, it is unclear how much of this correlation links with biomarkers of metabolism disorder. We have investigated the association between hypoglycaemic and fat profile with lung function in Indian diabetic subjects. DESIGN: Prospective observational study. SETTING: Diabetes care unit of King Edward Memorial (KEM) hospital. PATIENTS: Out of 465 patients who agreed to participate in this study, valid lung function data were available from 347 Type 2 diabetic subjects. MEASUREMENTS: Pulmonary function test including predicted forced vital capacity (% FVC), predicted forced expiratory volume in 1 second (% FEV1) and FEV1/FVC ratio were assessed. We also examined fat profile, glucose, HbA1c, hemoglobin and other hematological parameters. RESULTS: Four hundred sixty-five subjects aged 55 ± 11 participated in the study. Predicted forced vital capacity, % FEV1 and FEV1/FVC ratio was 85.88 ± 13.53, 85.87 ± 14.06 and 82.03 ± 6.83, respectively. Also, approximately 8 to 17% of the participant reported having at least one chronic respiratory symptom or lung disease. We found that high glycaemic measures (i.e. fasting and post-meal plasma glucose) are linked with dyspnea. In addition, HDL (high-density lipoprotein) concentration was directly associated with % FVC. CONCLUSIONS: It is difficult to draw a clear conclusion about the cause-effect relationship or clinical impact based on this study alone. However, identification of clinically meaningful elements for developing a screening program is critical.

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.

Peak flow meter with a questionnaire and mini-spirometer to help detect asthma and COPD in real-life clinical practice: a cross-sectional study.

Peak flow meter with questionnaire and mini-spirometer are considered as alternative tools to spirometry for screening of asthma and chronic obstructive pulmonary disease. However, the accuracy of these tools together, in clinical settings for disease diagnosis, has not been studied. Two hundred consecutive patients with respiratory complaints answered a short symptom questionnaire and performed peak expiratory flow measurements, standard spirometry with Koko spirometer and mini-spirometry (COPD-6). Spirometry was repeated after bronchodilation. Physician made a final diagnosis of asthma, chronic obstructive pulmonary disease and others. One eighty nine patients (78 females) with age 51 ± 17 years with asthma (115), chronic obstructive pulmonary disease (33) and others (41) completed the study. "Breathlessness > 6months" and "cough > 6months" were important symptoms to detect obstructive airways disease. "Asymptomatic period > 2 weeks" had the best sensitivity (Sn) and specificity (Sp) to differentiate asthma and chronic obstructive pulmonary disease. A peak expiratory flow of < 80% predicted was the best cut-off to detect airflow limitation (Sn 90%, Sp 50%). Respiratory symptoms with PEF < 80% predicted, had Sn 84 and Sp 93% to detect OAD. COPD-6 device under-estimated FEV1 by 13 mL (95% CI: -212, 185). At a cut-off of 0.75, the FEV1/FEV6 had the best accuracy (Sn 80%, Sp 86%) to detect airflow limitation. Peak flow meter with few symptom questions can be effectively used in clinical practice for objective detection of asthma and chronic obstructive pulmonary disease, in the absence of good quality spirometry. Mini-spirometers are useful in detection of obstructive airways diseases but FEV1 measured is inaccurate. CHRONIC LUNG DISEASES: DIFFERENTIATING CONDITIONS IN POORLY-EQUIPPED SETTINGS: A simple questionnaire and peak flow meter measurements can help doctors differentiate between asthma and chronic lung disease. In clinical settings where access to specialist equipment and knowledge is limited, it can be challenging for doctors to tell the difference between asthma and chronic obstructive pulmonary disease (COPD). To determine a viable alternative method for differentiating between these diseases, Rahul Kodgule and colleagues at the Chest Research Foundation in Pune, India, trialed a simplified version of two existing symptom questionnaires, combined with peak flow meter measurements. They assessed 189 patients using this method, and found it aided diagnosis with high sensitivity and specificity. Breathlessness, cough and wheeze were the minimal symptoms required for COPD diagnosis, while the length of asymptomatic periods was most helpful in distinguishing asthma from COPD.

A randomized, double-blind study comparing the efficacy and safety of a combination of formoterol and ciclesonide with ciclesonide alone in asthma subjects with moderate-to-severe airflow limitation.

CONTEXT: The combination of inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) is widely used in the treatment of moderate-to-severe asthma uncontrolled by ICS alone. AIMS: To evaluate the efficacy and safety of a new ICS-LABA combination inhaler containing Formoterol (F) and Ciclesonide (C). SETTINGS AND DESIGN: A double-blind, double-dummy, parallel group fashion, multi-centric study. SUBJECTS AND METHODS: A total of 169 asthma patients received Ciclesonide 80 µg once daily during a 4-week run-in period, after which, they were randomized to receive either C (80 µg) or a combination of F (4.5 µg) and C (80 µg) (FC) both delivered through a hydro-fluro-alkane pressurized-metered-dose inhaler as 1 puff twice daily, for 6 weeks. STATISTICAL ANALYSIS USED: Inter-group differences were compared using t-test for independent samples at a significance level of 5%. RESULTS: From baseline, the improvements in forced expiratory volume in 1 s at 1, 3, and 6 weeks was significantly higher in the FC group compared to Group C (110 ml vs. 40 ml, 140 ml vs. 20 ml, and 110 ml vs. 40 ml, respectively, all P < 0.05). From baseline, the improvements in mean morning peak expiratory flow at 1, 3, and 6 weeks was significantly higher in the FC group compared to Group C (17 L/min vs.-3 L/min, 22 L/min vs. 3 L/min, and 30 ml vs. 8 L/min respectively, all P < 0.05). The changes in symptom scores were similar in both the groups. The adverse events in the FC group were not significantly different from those in the C group. CONCLUSIONS: FC provides better improvement than C alone in terms of lung function and symptoms without increased risk of adverse events in asthma patients.

Asthma Insights and Management in India: Lessons Learnt from the Asia Pacific - Asthma Insights and Management (AP-AIM) Study.

BACKGROUND: Despite a better understanding of the pathophysiology of asthma, presence of reliable diagnostic tools, availability of a wide array of effective and affordable inhaled drugs and simplified national and international asthma management guidelines, asthma remains poorly managed in India. OBJECTIVE: The Asia-Pacific Asthma Insight and Management (AP-AIM) study was aimed at understanding the characteristics of asthma, current management, level of asthma control and its impact on quality of life across Australia, China, Hong Kong, India, Malaysia, Singapore, South Korea, Taiwan and Thailand. This paper describes the results of asthma management issues in India in detail and provides a unique insight into asthma in India. METHODOLOGY: The AP-AIM India study was conducted in eight urban cities in India, viz: Ajmer, Delhi, Kolkata, Rourkela, Chennai, Mangalore, Mumbai and Rajkot from February to July 2011. Face-to-face interviews were conducted in adult asthmatics and parents of asthmatic children between the ages of 12 and 17 years with a confirmed diagnosis or a treatment history of 1 year for asthma. RESULTS: Four hundred asthmatics (M:F::1:1.273), with a mean age of 50 ± 17.8 years, from across India were studied. 91% of the asthmatics in India perceived their asthma to be under control, however, none of the asthmatics had controlled asthma by objective measures. Asthmatics in India believed that their asthma was under control if they have up to 2 emergency doctor visits a year. The quality of life of these patients was significantly affected with 93% school/work absenteeism and a loss of 50% productivity. Seventy-five percent of the asthmatics have never had a lung function test. The common triggers for asthmatics in India were dust (49%) and air pollution (49%), while only 5% reported of pollen as triggers. Eighty-nine percent of Indian asthmatics reported an average use of oral steroids 10.5 times a year. Only 36% and 50% of Indian asthmatics used controller and rescue inhalers with a majority preferring the oral route of asthma medication. CONCLUSIONS: This study has clearly highlighted the fact that asthma management in India remains very poor, with a significant proportion of patients experiencing bothersome symptoms and worsened quality of life. There is a need for an urgent review of this situation and initiate active measures at local as well as national levels to improve asthma care in India.

Systemic inflammation (C-reactive protein) in type 2 diabetic patients is associated with ambient air pollution in Pune City, India.

OBJECTIVE: To study the association between ambient air pollutants and serum C-reactive protein (CRP) concentration in 1,392 type 2 diabetic patients in Pune, India. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted that linked daily time series of ambient air pollution data (obtained from central monitoring sites) and plasma CRP concentration in type 2 diabetic patients from the Wellcome Trust Genetic (WellGen) Study, recruited between March 2005 and May 2007. Air pollution effects on CRP concentration were investigated with delays (lags) of 0-7 days and multiday averaging spans of 7, 14, and 30 days before blood collection adjusted for age, sex, BMI, hemoglobin, fasting plasma glucose, treatment with agents with anti-inflammatory action, season, air temperature, and relative humidity. RESULTS: Median CRP concentration was 3.49 mg/L. For 1 SD increase in SO(2) and oxides of nitrogen (NO(x)) concentrations in ambient air, a day before blood collection (lag(1)), we observed a significant increase in CRP (9.34 and 7.77%, respectively). The effect was higher with lag(2) (12.42% for SO(2) and 11.60% for NO(x)) and wore off progressively thereafter. We also found a significant association with multiday averaging times of up to 30 and 7 days for SO(2) and NO(x), respectively. No significant associations were found between particulate matter with an aerodynamic profile ≤10 µm (PM(10)) and CRP concentration except in summer. The association was significantly higher among patients with a shorter duration of diabetes, and in those not on statin and thiazolidinedione treatment. CONCLUSIONS: We demonstrate, for the first time, a possible contribution of ambient air pollution to systemic inflammation in Indian type 2 diabetic patients. This may have implications for vascular complications of diabetes.

Chronic obstructive pulmonary disease in non-smokers.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Tobacco smoking is established as a major risk factor, but emerging evidence suggests that other risk factors are important, especially in developing countries. An estimated 25-45% of patients with COPD have never smoked; the burden of non-smoking COPD is therefore much higher than previously believed. About 3 billion people, half the worldwide population, are exposed to smoke from biomass fuel compared with 1.01 billion people who smoke tobacco, which suggests that exposure to biomass smoke might be the biggest risk factor for COPD globally. We review the evidence for the association of COPD with biomass fuel, occupational exposure to dusts and gases, history of pulmonary tuberculosis, chronic asthma, respiratory-tract infections during childhood, outdoor air pollution, and poor socioeconomic status.

Enhanced alpha1-adrenergic trophic activity in pulmonary artery of hypoxic pulmonary hypertensive rats.

Mechanisms that induce the excessive proliferation of vascular wall cells in hypoxic pulmonary hypertension (PH) are not fully understood. Alveolar hypoxia causes sympathoexcitation, and norepinephrine can stimulate alpha(1)-adrenoceptor (alpha(1)-AR)-dependent hypertrophy/hyperplasia of smooth muscle cells and adventitial fibroblasts. Adrenergic trophic activity is augmented in systemic arteries by injury and altered shear stress, which are key pathogenic stimuli in hypoxic PH, and contributes to neointimal formation and flow-mediated hypertrophic remodeling. Here we examined whether norepinephrine stimulates growth of the pulmonary artery (PA) and whether this is augmented in PH. PA from normoxic and hypoxic rats [9 days of 0.1 fraction of inspired O(2) (Fi(O(2)))] was studied in organ culture, where wall tension, Po(2), and Pco(2) were maintained at values present in normal and hypoxic PH rats. Norepinephrine treatment for 72 h increased DNA and protein content modestly in normoxic PA (+10%, P < 0.05). In hypoxic PA, these effects were augmented threefold (P < 0.05), and protein synthesis was increased 34-fold (P < 0.05). Inferior thoracic vena cava from normoxic or hypoxic rats was unaffected. Norepinephrine-induced growth in hypoxic PA was dose dependent, had efficacy greater than or equal to endothelin-1, required the presence of wall tension, and was inhibited by alpha(1A)-AR antagonist. In hypoxic pulmonary vasculature, alpha(1A)-AR was downregulated the least among alpha(1)-AR subtypes. These data demonstrate that norepinephrine has trophic activity in the PA that is augmented by PH. If evident in vivo in the pulmonary vasculature, adrenergic-induced growth may contribute to the vascular hyperplasia that participates in hypoxic PH.