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Objective: In this document, 9 Indian experts have evaluated the factors specific to LMICs when it came to Severe Asthma (SA) diagnosis, evaluation, biologic selection, non-biologic treatment options, and follow-up., Data Sources: A search was performed using 50 keywords, focusing on the Indian/LMICs perspective, in PubMed, Cochrane Library, and Google Scholar. The key areas of the search were focused on diagnosis, phenoendotyping, non-biological therapies, selecting a biologic, assessment of treatment response, and management of exacerbation., Study Selections: The initial search revealed 1826 articles, from these case reports, observational studies, cohort studies, non-English language papers, etc., were excluded and we short-listed 20 articles for each area. Five relevant articles were selected by the experts for review., Results: In LMICs, SA patients may be referred to the specialist for evaluation a little late for Phenoendotyping of SA. While biologic therapy is now a standard of care, pulmonologists in LMICs may not have access to all the investigations to phenoendotype SA patients like fractional exhaled nitric oxide (FeNO), skin prick test (SPT), etc., but phenotyping of SA patients can also be done with simple blood investigations, eosinophil count and serum immunoglobulin E (IgE). Choosing a biologic in the overlapping phenotype of SA and ACO patients is also a challenge in the LMICs., Conclusions: Given the limitations of LMIC, it is important to select the right patient and explain the potential benefits of biological therapy. Non-biologic add-on therapies can be attempted in a resource-limited setting where biological therapy is not available/feasible for patients.

Objectives: Asthma is characterised by chronic airway inflammation and remodelling. Inflammation may alter the thermal balance of the affected tissues secondary to changes in the blood flow. Measurement of exhaled breath temperature (EBT) is a simple, safe and non-invasive technique to detect airway inflammation. The objective of this study was to measure EBT in asthma patients and compare it with healthy controls and also to correlate it with serum biomarkers of inflammation and remodelling., Methods: 24 male asthma patients and 23 age and gender matched healthy controls were recruited in the study. EBT and core body temperature were recorded followed by spirometry to measure forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR). Serum levels of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were quantified by ELISA., Results: Asthmatics had significantly lower FEV1% predicted compared to healthy subjects. EBT in asthma patients was significantly higher as compared to healthy controls while rate of rise of EBT was not significantly different. Serum biomarker of inflammation i.e. IL-6 and of tissue remodelling i.e. VEGF, MMP-9 and TIMP-1 were significantly raised in asthma patients while the ratio of MMP-9/TIMP-1 was comparable between two groups. But no correlation was observed between EBT and serum biomarkers., Conclusion: EBT may be used as an adjunct tool for non-invasive assessment of airway inflammation and remodelling in asthma patients., (© Journal of the Association of Physicians of India 2011.)

Bronchial asthma is an important public health problem in India with significant morbidity. Several international guidelines for diagnosis and management of asthma are available, however there is a need for country-specific guidelines due to vast differences in availability and affordability of health-care facilities across the globe. The Indian Chest Society (ICS) and the National College of Chest Physicians (NCCP) of India have collaborated to develop evidence-based guidelines with an aim to assist physicians at all levels of health-care in diagnosis and management of asthma in a scientific manner. Besides a systematic review of the literature, Indian studies were specifically analysed to arrive at simple and practical recommendations. The evidence is presented under these five headings: (1) definitions, epidemiology and impact, (2) diagnosis, (3) pharmacologic management of stable disease, (4) management of acute exacerbations, and (5) non-pharmacologic management and special situations. The modified grade system was used for classifying the quality of evidence as 1, 2, 3, or usual practice point (UPP). The strength of recommendation was graded as A or B depending upon the level of evidence.

Background and Objective: The quality of life (QOL) and autonomy preferences of asthmatics in developing countries have been sparingly researched, with a resulting lack of management strategies. This study determined the asthma-specific QOL and autonomy preferences of a population of asthmatics in a developing country and their association with relevant sociodemographic and clinical characteristics., Methods: A cross-sectional study using the Asthma Quality of Life Questionnaire and the Asthma Autonomy Questionnaire was performed on a population of stable asthmatics recruited from a tertiary care centre in India. Severity of the disease was assessed by spirometry., Results: The study population comprised 80 asthmatics. The mean (SD) overall QOL score was 5.04 (0.97). This was significantly associated with history of hospitalization during the previous year for an asthma attack (P < 0.01) and with FEV(1) (P < 0.05) on univariate analysis; on multivariate analysis, only history of hospitalization was significant. Autonomy preferences of the patients showed higher scores for information-seeking (mean (SD) = 78.95 (16.35) ) than decision-making (mean (SD) = 38.21 (14.6)). The information-seeking preferences had a negative correlation with age (P < 0.01) and a positive correlation with education status (P < 0.01) and decision-making correlated with education status (P < 0.05). A minority of patients (19%) indicated a preference for a greater say in decision-making than their physicians. There was a lower tendency for decision-making when given a 'severe exacerbation' scenario than in 'mild exacerbation' (P < 0.001) or 'stable disease' (P < 0.001)., Conclusions: Hospitalization history and FEV(1) values are the parameters having the most significant impact on the QOL of asthmatics. There is a clear desire to obtain more information about the disease but most patients do not endorse the idea of making independent disease-related decisions.

Mycoplasma pneumoniae (M pneumoniae), primarily recognised as a causative agent of community-acquired pneumonia has recently been linked to asthma. An infection with M pneumoniae may precede the onset of asthma or exacerbate asthma symptoms. Chronic infection with M pneumoniae has been suspected to play a part in some patients with asthma. The role of immunoglobulin E-related hypersensitivity and induction of T helper type 2 immune response leading to inflammatory response in M pneumoniae-infected patients with asthma have also been proposed. Use of macrolides in reducing asthma symptoms only in M pneumoniae-infected patients supports the use of macrolides in patients with asthma having M pneumoniae infection. As macrolides are both antimicrobial and anti-inflammatory drugs, the therapeutic role of their biphasic nature in reducing asthma symptoms needs further attention in clinical research.

Introduction: The beta(2)-adrenergic receptor (ADRB2) polymorphisms are known to be functionally relevant and disease modifying in subjects with asthma. However, the association of these polymorphisms with asthma remains to be established. Our objective is to investigate the association of the ADRB2 polymorphisms and haplotypes with asthma in North Indian subjects., Methods: A subset of 101 unrelated cases and 55 unrelated unaffected individuals were used for a case-control disease-association test., Results: Ten variable single nucleotide polymorphism (SNP) sites within a span of 2.193 kb were identified in the ADRB2 gene by the sequencing and genotyping of 351 bronchial asthma patients and healthy individuals. The distributions of genotype and allele frequencies for individual SNPs in the ADRB2 gene and ADRB2 haplotype frequencies were estimated in unrelated asthmatics and healthy individuals. No significant association was observed between ADRB2 genotypes and alleles with disease status after Bonferroni correction for multiple testing (reference p value = 0.0083). However, haplotype GGCTTTGCAA was found to be significantly associated with asthma (p = 0.021) in the studied population., Conclusion: Our results suggest that there is likely to be a functional significance of the ADRB2 gene with asthma.

Introduction: The beta(2)-adrenergic receptor (beta(2)AR or ADRbeta(2)) is the target for beta(2)-agonist drugs used for bronchodilation in asthma and other respiratory diseases. The aim of this study was to identify common single nucleotide polymorphisms (SNPs) and haplotypes in asthmatics and healthy individuals from an Indian population, and determine the influence of beta(2)AR SNPs in responsiveness to beta(2)-agonist therapy in asthma patients., Methods: Ten variable SNP sites within a span of 2.193 kb were identified in the beta(2)AR gene by sequencing and genotyping 374 bronchial asthma patients and healthy individuals from an Indian population. Spirometry tests were performed on 80 unrelated patients before and after administration of 200 microg of salbutamol. A post-bronchodilator forced expiratory volume in one second (FEV(1)) change of >or= 15.3% was considered a good response, and a change of<15.3% was defined as a poor response, to salbutamol., Results: The pattern of linkage disequilibrium between the ten SNPs showed a single, linked SNP block consisting of sites -468, -367, -47, -20, and 79 having strong linkage disequilibrium, while the SNPs at sites -1023, -654, 46, 252, and 523 showed very low linkage with one another and with the linked region. The SNPs were found to be organized into 16 haplotypes in the studied population. We found that patients with a homozygous Arg-16 form at nucleotide position 46 are poor responders with probability of 0.81, and patients with a homozygous Gly-16 form are good responders with a probability of 0.73. The responder status to salbutamol treatment and the genotype at nucleotide position 46 in beta(2)AR gene of an asthmatic patient are significantly associated in the studied Indian population (chi2=9.98, df=2, p=0.0068). Most importantly, this association for responsiveness to salbutamol at nucleotide position 46 is independent of other SNPs in the beta(2)AR gene., Conclusion: This study suggests that the SNP at nucleotide position 46 has particular relevance to pharmacogenetics in the Indian population studied.

Background & Objectives: Asthma is now regarded as an inflammatory disease and bronchial inflammation may disrupt mucociliary function. Inhaled drugs may act by improving mucociliary function. The aim of the study was to investigate the effect of salbutamol, ipratropium bromide and beclomethasone on mucociliary clearance in patients with chronic stable asthma and to compare the efficacy of these drugs on mucociliary clearance., Methods: Ten patients with chronic stable asthma were enrolled in the study, but two patients did not complete the study. Patients with bronchial asthma were chosen on clinical grounds. (99m)Tc phytate radioaerosol generated through a nebulizer, was given to each patient on four days. After each administration the radioactivity over the thorax was constantly measured in sequential frame mode for 120 min. Radioactivity in the thorax was also measured after 24 h. A base-line pulmonary function test with reversibility was obtained. Salbutamol, ipratropium bromide, beclomethasone dipropionate and placebo inhalation were given randomly to each patient on four days., Results: The mean age of patients (n = 8) was 36 +/- 9.3 yr and mean duration of symptoms was 5 +/- 6.6 yr. There was no visual impression that mucociliary clearance was enhanced with any of the drugs. The time activity curves did not show any visually recognisable change in slope. In only one patient the curve tended to show a steeper slope with ipratropium inhalation. In the rest of the patients the curves showed no difference at all with medication when compared with placebo. All the quantitative indices analyzed by two-way ANOVA at the end of one and two hours were comparable for the three test drugs and placebo. None of the three test drugs demonstrated statistically significant mucociliary clearance effect compared with placebo. However, the temporal difference in airways clearance efficiency (ACE) was significant with beclomethasone and ipratropium bromide., Interpretation & Conclusion: Inhalation of any of the three drugs tested did not produce any immediate improvement in mucociliary clearance as compared to placebo in patients with stable bronchial asthma suggesting the need for further studies using higher doses of drugs for longer duration in a large sample.

Theophylline clearance is altered by many drugs and diseases that may be associated with undernutrition. Therefore, we studied theophylline clearance in 12 undernourished [body mass index (BMI) less than 19] and 12 well nourished asthma patients (body mass index more than 19). Uncoated theophylline tablet (200 mg, 300 mg dose 5 mg/kg approx) was administered orally to each asthma patient after 12 hours overnight fasting. Serum theophylline concentrations were estimated after 2, 4, 6, 8 hours of drug administration and it was calculated from log conc: time curve. Undernourished asthma patients had a mean theophylline clearance of 85.6 (SE = 6.2) ml/hr/kg while it was 125.6 (SE = 3.8) ml/hr/kg in well-nourished asthma patients. The difference between two groups was highly significant (p < 0.01). We conclude that theophylline clearance is significantly lower in undernourished asthma patients and they will require a lower maintenance dose of theophylline.

Various reports indicate significant intersubject variation in the rate of absorption of controlled release theophylline products that are commercially available. Serum theophylline concentration was estimated in 17 asthma patients treated with controlled release theophylline tablet (mean dose: 5.6 +/- 0.6 mg/kg, mean body wt: 49.82 +/- 9.05 kg). The mean maximal concentration (Cmax) of 5.57 +/- 1.65 micrograms/ml occurred at mean time of maximal concentration (Tmax) of 3.3 +/- 1.36 (mean +/- SD) hours. Mean minimal concentration (Cmin) was 3.164 +/- 1.1 micrograms/ml (mean +/- SD) at mean time of minimal concentration (Tmin) of 5.77 +/- 1.77 (mean +/- SD) hours. The mean percent fluctuation was 112.95 +/- 183.45 (mean +/- SD) but in 4 out of 17 patients, percent fluctuation was 107.29 to 823.10. Therefore, 23.5% patients treated with controlled release theophylline tablet had wide fluctuations in serum theophylline concentration.

"The concept of yoga is helpful for the treatment of Bronchial Asthma", has created a great interest in the medical research field. In order to investigate whether autonomic functions and pulmonary functions are improved in asthma patients after short term yoga training, a study was conducted with nine diagnosed bronchial asthma patients. Yoga training was given for seven days in a camp in Adhyatma Sadhna Kendra, New Delhi. The autonomic function tests to measure the parasympathetic reactivity (Deep Breathing test, Valsalva Manouever), Sympathetic reactivity (Hand Grip test, Cold Pressure test), and pulmonary function tests FVC, FEV1, PEFR, PIF, BHT and CE were recorded before and after yoga training. The resting heart rate after yoga training (P < 0.05) was significantly decreased (89.55 +/- 18.46/min to 76.22 +/- 16.44/min). The sympathetic reactivity was reduced following yoga training as indicated by significant (P < 0.01) reduction in DBP after HGT. There was no change in parasympathetic reactivity. The FVC, FEV1, PEFR did not show any significant change. The PIF (P < 0.01), BHT (P < 0.01) and CE (P < 0.01) showed significant improvement. The results closely indicated the reduction in sympathetic reactivity and improvement in the pulmonary ventilation by way of relaxation of voluntary inspiratory and expiratory muscles. The "comprehensive yogic life style change programme for patients of Bronchial Asthma" have shown significant benefit even within a short period.

Objectives : The combination of a 43-2 agonist and an anticholinergic agent is of-ten used to manage bronchial asthma. However, it is unclear whether these drugs should be given separately in sequence or in a fixed dose combination for maximum effect. Methods : 27 patients with stable bronchial asthma were given the above two drugs in two separate sessions one week apart. In one session they were given the above two drugs as a fixed dose combination and in the other session, they were given se-quentially with salbutamol following ipratropium after 30 minutes. Spirometry was performed at baseline and 15, 30 and 60 minutes after inhaling the second drug. Results : Both groups showed significant improvement in forced vital capacity (FVC), forced expiratory time in one second (FEV 1 ), peak expiratory flow rate (PEFR) and forced expiratory flow (FEF 25-75 ) from baseline upto one hour. FVC increased initially and then stabilized; however, the increase was more sustained in the group getting combination treatment. This group also showed a higher rise in FEV 1 (p=0.02). Both FEV 1 and FEF 25-75 decreased after 30 minutes in the group that received sequential therapy. PEFR increased continuously till 60 minutes in both groups and there was no significant difference between them (p=0.98). Interpretation and Conclusion: Both methods of drug dosing produce equivalent bronchodilation. Fixed dose combinations produced a more sustained rise in FVC and higher increase in FEV 1 . Hence fixed dose combinations are more effective short-term bronchodilators and give an added advantage of reducing the number of inhalers required, thus improv-ing compliance.

Allergic bronchopulmonary aspergillosis ( ABPA) is an immunological pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus, manifesting with poorly controlled asthma, recurrent pulmonary infiltrates and bronchiectasis . There are estimated to be in excess of four million patients affected world-wide. The importance of recognizing ABPA relates to the improvement of patient symptoms, and delay in development or prevention of bronchiectasis, one manifestation of permanent lung damage in ABPA. Environmental factors may not be the only pathogenetic factors because not all asthmatics develop ABPA despite being exposed to the same environment. Allergic bronchopulmonary aspergillosis is probably a polygenic disorder, which does not remit completely once expressed, although long-term remissions do occur. In a genetically predisposed individual, inhaled conidia of A. fumigatus germinate into hyphae with release of antigens that activate the innate and adaptive immune responses (Th2 CD4+ T cell responses) of the lung. The International Society for Human and Animal Mycology ( ISHAM) has constituted a working group on ABPA complicating asthma (www.abpaworkinggroup.org), which convened an international conference to summarize the current state of knowledge, and formulate consensus-based guidelines for diagnosis and therapy. New diagnosis and staging criteria for ABPA are proposed. Although a small number of randomized controlled trials have been conducted, long-term management remains poorly studied. Primary therapy consists of oral corticosteroids to control exacerbations, itraconazole as a steroid-sparing agent and optimized asthma therapy. Uncertainties surround the prevention and management of bronchiectasis, chronic pulmonary aspergillosis and aspergilloma as complications, concurrent rhinosinusitis and environmental control. There is need for new oral antifungal agents and immunomodulatory therapy. [ABSTRACT FROM AUTHOR]