Clinical outcomes of bronchiectasis in India: data from the EMBARC/Respiratory Research Network of India registry.

BACKGROUND: Identifying risk factors for poor outcomes can help with risk stratification and targeting of treatment. Risk factors for mortality and exacerbations have been identified in bronchiectasis but have been almost exclusively studied in European and North American populations. This study investigated the risk factors for poor outcome in a large population of bronchiectasis patients enrolled in India. METHODS: The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India (EMBARC-India) registry is a prospective observational study of adults with computed tomography-confirmed bronchiectasis enrolled at 31 sites across India. Baseline characteristics of patients were used to investigate associations with key clinical outcomes: mortality, severe exacerbations requiring hospital admission, overall exacerbation frequency and decline in forced expiratory volume in 1 s. RESULTS: 1018 patients with at least 12-month follow-up data were enrolled in the follow-up study. Frequent exacerbations (≥3 per year) at baseline were associated with an increased risk of mortality (hazard ratio (HR) 3.23, 95% CI 1.39-7.50), severe exacerbations (HR 2.71, 95% CI 1.92-3.83), future exacerbations (incidence rate ratio (IRR) 3.08, 95% CI 2.36-4.01) and lung function decline. Coexisting COPD, dyspnoea and current cigarette smoking were similarly associated with a worse outcome across all end-points studied. Additional predictors of mortality and severe exacerbations were increasing age and cardiovascular comorbidity. Infection with Gram-negative pathogens (predominantly Klebsiella pneumoniae) was independently associated with increased mortality (HR 3.13, 95% CI 1.62-6.06), while Pseudomonas aeruginosa infection was associated with severe exacerbations (HR 1.41, 95% CI 1.01-1.97) and overall exacerbation rate (IRR 1.47, 95% CI 1.13-1.91). CONCLUSIONS: This study identifies risk factors for morbidity and mortality among bronchiectasis patients in India. Identification of these risk factors may support treatment approaches optimised to an Asian setting.

Assessing physical and chemical properties of saliva among tuberculosis patients on anti-tuberculosis treatment - An observational study.

Background: Tuberculosis (TB) is one of the major systemic conditions which is a preventable and curable infection but remains a significant cause of death. The WHO, in its global plan to stop TB reports, that poor treatment has resulted in the evolution of Mycobacterium tuberculosis strains that do not respond to treatment with the standard first-line combination of anti- tuberculosis medicines, resulting in the emergence of multidrug-resistant tuberculosis in almost every country of the world.The present study was aimed to assess the physical and chemical property of stimulated and unstimulated saliva and identify if any association exist with alterations in taste perception in patients with antituberculosis medications. Methods: A total of 30 patients on anti-tuberculosis drugs were considered as cases and 30 healthy volunteers were considered as controls and included in the study. All study subjects were assessed for their physical property like flow rate, viscosity, pH and chemical property like sodium, potassium, calcium, phosphorous of stimulated and unstimulated saliva. All the subjects on Anti-tuberculosis drugs were assessed for change in taste perceptions using the standard questionnaire. Results: There is a significant decrease in the flow rate (0.34 ±â€¯0.06) and pH (5.89 ±â€¯0.37) of unstimulated saliva of patients and the flow rate (0.38 ±â€¯0.07) and viscosity (1.34 ±â€¯0.28) of stimulated saliva among the case group compare to the control group. All the electrolytes' concentrations such as sodium, potassium, calcium, and phosphorous values were significantly altered in stimulated and unstimulated saliva of the case group compared to the control group in which p-value < 0.05 was considered. Conclusion: There are significant changes in physical and chemical properties of both stimulated and unstimulated saliva which has an effect on taste perception inpatient with anti-tuberculosis medications. Hence, salivary flow rate, pH, viscosity, and salivary electrolytes of tuberculosis patients should be considered as important parameters in guiding the diet, so that there will be an improvement in their taste perception and medication protocol, thus maintaining their nutritional status which leads to improving their health.

Pilot study investigating diagnostic utility of serum MMP-1 and TGF-ß1 in asthma in 'real world' clinical practice in India.

AIMS: At a tissue level, matrix metalloproteinase-1 (MMP-1) and transforming growth factor-beta 1 (TGF-ß1) contribute to allergic airway inflammation, tissue remodelling and disease severity in asthma via different pathways. Their peripheral blood levels and role in diagnosis and therapeutic monitoring has not been adequately explored. We investigated the association between MMP-1 and TGF-ß in moderate and severe persistent asthma and evaluated their performance characteristics by constructing receiver operating characteristic curves. METHODS: Serum MMP-1 and TGF-ß1 were measured using ELISA in 75 adults; moderate persistent asthma (n=25), severe persistent asthma (n=25) and healthy community controls (n=25). Severity of asthma was determined as per Global Initiative for Asthma guidelines. Subjects were followed up for 3 months and treatment responsiveness was assessed by spirometry and symptom response. RESULTS: Serum MMP-1 and TGF-ß1 were significantly elevated in asthmatics compared with controls (p<0.0001 and p<0.01). While serum MMP-1 was elevated in severe asthma compared with moderate asthma (p<0.05), TGF-ß1 was lower in severe asthma compared with moderate asthma (p<0.05). The performance characteristics of serum MMP-1 and TGF-ß1 were promising in this cohort with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 82%, 100%, 100% and 99% and 62%, 100%, 100% and 97.8%, respectively; sensitivity of MMP-1 being superior. CONCLUSION: This pilot study showed that serum MMP-1 and TGF-ß1 levels are elevated in chronic asthma and may serve as a useful adjunct in differentiating moderate from severe asthma. A large multicentre study in well characterised cohort of asthmatics is warranted to investigate their role in diagnosis and therapeutic monitoring.

Haplotype analysis of ADAM33 polymorphisms in asthma: A pilot study.

Background & objectives: ADAM33 is implicated as a potentially strong candidate gene for asthma and bronchial hyper-responsiveness. Many polymorphisms of ADAM33 have been studied along with ADAM33 expression in various cells of the lungs. Haplotype analysis also showed association with asthma in different populations across the world. Therefore, the aim of this study was to perform a comprehensive screening of ADAM33 polymorphisms in adult patients with asthma. Methods: Thirty five polymorphisms of ADAM33 were genotyped in 55 patients with asthma and 53 controls. The association of single nucleotide polymorphisms (SNPs) and haplotypes with phenotypes of asthma was analysed. Results: The genotype, minor allele frequency, odds ratio and Hardy-Weinberg equilibrium did not show any significant difference among cases and controls. No association was found between SNPs of ADAM33 with the severity of asthma. Correlation analysis of ADAM33 SNPs to the phenotypes, based on clinical variables and allergen sensitization, did not show significant difference. Haplotype analysis showed that rs2280090 and rs2280091 were associated with asthma in the patient group. Interpretation & conclusions: Haplotype analysis showed an association of the two SNP variations with asthma. These SNPs lead to amino acid change and are prone to phosphorylation, which may affect expression levels and protein function of ADAM33 and asthma susceptibility.

Factors influencing severity of community-acquired pneumonia.

INTRODUCTION: Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality in India. There is a need to understand the risk factors associated with severity of CAP in our population. This study was part of the international global initiative for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia study to evaluate MRSA. METHODS: A total of 100 consecutive cases of pneumonia admitted to the Department of Pulmonary Medicine in a tertiary care hospital were recruited in the study during March-July 2015. The severity of pneumonia was assessed based on the CURB-65 score. Individuals with pneumonia and CURB-65 score >2 were compared with subjects with CURB-65 score ≤2. Individuals were also evaluated for the causative organism and its resistance pattern with specific reference to the presence of MRSA. RESULTS: Mean age of patients was 54.03 years, 66% were men. Patients were managed either in the intensive care unit (42%) or wards/high dependency unit (58%), 22% needed noninvasive ventilation and 18% needed mechanical ventilation within 24 h of admission. On multivariate analysis, prior respiratory infection (within last 1 year), obesity (body mass index >30), and alcoholism, old age (>60 years) were independently associated risk factors for severe pneumonia. There were no cases of MRSA. In 34% of cases, organisms could be identified. Most common organisms were Klebsiella (8%), influenza (8%), and Pseudomonas (5%). CONCLUSION: Prior respiratory infection, obesity, alcoholism, and old age (>60 years) were observed to be important risk factors for severe CAP. Prospective studies should evaluate effect of weight reduction and cessation of alcohol consumption on recurrences of pneumonia in this population and on the severity of pneumonia.

Antibiotic Prescription, Organisms and its Resistance Pattern in Patients Admitted to Respiratory ICU with Respiratory Infection in Mysuru.

AIM OF STUDY: Respiratory infections account for significant morbidity, mortality and expenses to patients getting admitted to ICU. Antibiotic resistance is a major worldwide concern in ICU, including India. It is important to know the antibiotic prescribing pattern in ICU, organisms and its resistance pattern as there is sparse data on Indian ICUs. MATERIALS AND METHODS: We conducted a prospective study from August 2015 to February 2016. All patients getting admitted to RICU with respiratory infection who were treated with antibiotics were included into study. Demographic details, comorbidities, Clinco-pathological score (CPI) on day1 and 2 of admission, duration of ICU admission, number of antibiotics used, antibiotic prescription, antimicrobial resistance pattern of patients were collected using APRISE questionnaire. RESULTS: During study period 352 patients were screened and 303 patients were included into study. Mean age was 56.05±16.37 and 190 (62.70%) were men. Most common diagnosis was Pneumonia (66%). Piperacillin-tazobactam was most common empirical antibiotic used. We found 60% resistance to piperacillin-tazobactam. Acinetobacter baumanii was the most common organism isolated (29.2%) and was highly resistant to Carbapenem (60%). Klebsiella pneumoniae was resistant to Amikacin (45%), piperacillin (55%) and Ceftazidime (50%). CONCLUSION: Piperacillin-tazobactam was the most common antibiotic prescribed to patients with respiratory infection admitted to ICU. More than half of patients (60%) had resistance to the empirical antibiotic used in our ICU, highlighting the need for antibiogram for each ICU. Thirty six percent of patient had prior antibiotic use and had mainly gram negative organisms with high resistance to commonly used antibiotics.

Linoleic acid metabolite leads to steroid resistant asthma features partially through NF-κB.

Studies have highlighted the role of nutritional and metabolic modulators in asthma pathobiology. Steroid resistance is an important clinical problem in asthma but lacks good experimental models. Linoleic acid, a polyunsaturated fatty acid, has been linked to asthma and glucocorticoid sensitivity. Its 12/15-lipoxygenase metabolite, 13-S-hydroxyoctadecadienoic acid (HODE) induces mitochondrial dysfunction, with severe airway obstruction and neutrophilic airway inflammation. Here we show that HODE administration leads to steroid unresponsiveness in an otherwise steroid responsive model of allergic airway inflammation (AAI). HODE treatment to allergic mice further increased airway hyperresponsiveness and goblet metaplasia. Treatment with dexamethasone was associated with increased neutrophilic inflammation in HODE treated allergic mice; unlike control allergic mice that showed resolution of inflammation. HODE induced loss of steroid sensitivity was associated with increased p-NFkB in mice and reduced GR-α transcript levels in cultured human bronchial epithelia. In summary, HODE modifies typical AAI to recapitulate many of the phenotypic features seen in severe steroid unresponsive asthma. We speculate that since HODE is a natural metabolite, it may be relevant to the increased asthma severity and steroid insensitivity in patients who are obese or consume high fat diets. Further characterization of HODE induced steroid insensitivity may clarify the mechanisms.

IL-10 and IL-17F Promoter Single Nucleotide Polymorphism and Asthma: A Case-Control Study in South India.

BACKGROUND: Several studies have assessed the association between IL-17F and IL-10 promoter polymorphisms and asthma, but the results were conflicting. Furthermore, few studies have evaluated the association of cytokine polymorphisms with asthma and its clinical phenotypes. OBJECTIVE: This study was conducted to evaluate the association of IL-10 (interleukin 10) and IL-17F (interleukin 17F) promoter polymorphisms (rs1800871, rs1800896 and rs1889570) with asthma and its clinical phenotypes including severity, atopic status, spirometric parameters, and response to treatment in south Indian population. A sub-study was conducted to assess cytokine levels in subjects with different gene variants. METHODS: IL-10 and IL-17F polymorphisms were genotyped in 419 asthmatic patients and 393 controls using Mass ARRAY. RESULTS: Our results showed an association between IL-10 SNPs and mild asthma. No association was found with any of three SNPs in moderate to severe asthma. Comparison of genotype distribution of IL-17F rs1887570 AA variant among atopic and non-atopic patients showed significant difference (p = 0.024). Correlation analysis of IL-10 and IL-17F SNPs to clinical variables showed a positive correlation between IL-17F rs1887570 AA and number of allergen sensitized (rs = 0.142, p = 0.004). Significant improvement in lung function was observed after 2 months of ICS (Inhaled corticosteroids) and LABA (long acting ß2 agonist) treatment in all subjects with no statistically significant difference among SNPs variants. Cytokines levels were similar in different SNP variants. CONCLUSION: We observed an association between IL-10 rs1800871 and rs1800896 SNPs and mild asthma, as well as IL-17F rs1887570 AA variant and number of allergens sensitized.

Variation in the prevalence of chronic bronchitis among smokers: a cross-sectional study.

OBJECTIVE: Given the wide variations in prevalence of chronic obstructive pulmonary disease observed between populations with similar levels of exposure to tobacco smoke, we aimed to investigate the possibility of variations in prevalence of chronic bronchitis (CB) between two geographically distinct smoking populations in rural Karnataka, India. DESIGN: The Burden of Obstructive Lung Disease (BOLD) questionnaire was administered to all men aged >30 years in a cross-sectional survey. The χ(2) and Fisher's exact tests were used to compare CB prevalence in the two populations. Logistic regression was used to analyse the impact of multiple variables on the occurrence of CB. RESULTS: Two samples of 2322 and 2182 subjects were included in the study. In non-smokers, CB prevalence did not differ between the populations. However, it was significantly different between smoking populations (44.79% vs. 2.13%, P < 0.0001). Logistic regression indicated that, in addition to smoking, region, age, occupational dust exposure and type of house were associated with higher likelihood of CB. An interaction between smoking and area of residence was found (P < 0.001) and appeared to explain the effect of region (without interaction). CONCLUSION: A significant difference in CB prevalence was observed between male populations from two areas of Karnataka state, including when stratified by smoking status. No significant difference was observed between non-smokers.