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.

Role of Neutrophil to Lymphocyte Ratio in Predicting Severity of Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) has been linked to and is associated with increased cardiovascular and cerebrovascular morbidity. Ongoing inflammatory responses play an important role in this association. Systemic inflammation is important in pathophysiology of OSA and its comorbidity. In this study, we aimed to evaluate the role of neutrophil-to-lymphocyte ratio (NLR) in OSA patients and comparing with other well-known inflammatory marker, C-reactive protein (CRP) along with thyroid-stimulating hormone(TSH) and body-mass index(BMI). We conducted a retrospective analysis of 162 patients with OSA and divided them into 2 categories based on apnea-hypopnea index (AHI) (< 30 and > = 30), and recorded their leukocyte profiles, sex, age and body mass index. 80 matched healthy controls were taken. Patients were excluded if they had underlying cancer, chronic inflammatory disease, any systemic infection, uncontrolled hypertension and diabetes mellitus, a known acute coronary syndrome, valvular heart disease, renal or hepatic dysfunction. We found that N/L Ratio in severe OSA patients was significantly higher compared with mild and moderate OSA patients and healthy controls (p < 0.001). CRP levels were not different in all OSA stages (p = 0.595). We noted a significant difference in mean BMI of the two groups. In the wake of increase in prevalence of OSA in a developing country like India coupled with inadequate proportion of sleep labs, NLR is an inexpensive, easy to obtain, widely available marker of inflammation that might in combination with other markers assist in identifying patients with severe OSA.

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.

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.

Identification of a threshold for biomass exposure index for chronic bronchitis in rural women of Mysore district, Karnataka, India.

BACKGROUND & OBJECTIVES: Exposure to air pollution due to combustion of biomass fuels remains one of the significant risk factors for chronic respiratory diseases such as chronic bronchitis. There is a need to identify the minimum threshold level of biomass index that is significantly associated with chronic bronchitis. This study was undertaken to identify a threshold for biomass exposure index in a rural women population in Mysore district, south India. METHODS: A cross-sectional survey was conducted in a representative population of Mysore and Nanjangud taluks. Eight villages each from Mysore and Nanjangud were randomly selected based on the list of villages from census 2001. A house-to-house survey was carried out by trained field workers using the Burden of Obstructive Diseases questionnaire, which evaluated the biomass smoke exposure and chronic bronchitis. All the women aged above 30 yr were included in the study. RESULTS: A total of 2011 women from Mysore and 1942 women from Nanjangud participated in the study. All women were non-smoking and used biomass fuels as the primary fuel for cooking. A threshold of biomass fuel exposure of 60 was identified on multivariate analysis in Mysore district after adjusting for age, passive smoking and working in a occupational exposure to dust, as the minimum required for a significant association with chronic bronchitis. One in every 20 women in Mysore district exposed to biomass fuel exposure index of 110 or more developed chronic bronchitis. INTERPRETATION & CONCLUSIONS: The minimum threshold of biomass exposure index of 60 is necessary to have a significant risk of developing chronic bronchitis in women. The number needed to harm to develop chronic bronchitis reduces with increasing biomass exposure index and women residing in rural Nanjangud have a higher risk for developing chronic bronchitis as compared to women in Mysore.

Factors affecting 30-month survival in lung cancer patients.

BACKGROUND & OBJECTIVES: Age adjusted incidence rate of lung cancer in India ranges from 7.4 to 13.1 per 100,000 among males and 3.9 to 5.8 per 100,000 among females. The factors affecting survival in lung cancer patients in India are not fully understood. The current study was undertaken to evaluate the factors affecting survival in patients diagnosed with lung cancer attending a tertiary care cancer institute in Bangalore, Karnataka, India. METHODS: Consecutive patients with primary lung cancer attending Bangalore Institute of Oncology, a tertiary care centre at Bangalore, between 2006 and 2009 were included. Demographic, clinical, radiological data were collected retrospectively from the medical records. RESULTS: A total of 170 consecutive subjects (128 males, 42 females) diagnosed to have lung cancer; 151 non-small cell lung cancer (NSCLC) and 19 small cell lung cancer (SCLC) were included. A higher proportion of never-smokers (54.1%) were observed, mostly presenting below the age of 60 yr. Most subjects were in stage IV and III at the time of diagnosis. More than 50 per cent of patients presented with late stage lung cancer even though the duration of symptoms is less than 2 months. The 30-month overall survival rates for smokers and never-smokers were 32 and 49 per cent, respectively. No significant differences were observed in 30 month survival based on age at presentation, gender and type of lung cancer. Cox proportional hazards model identified never-smokers and duration of symptoms less than 1 month as factors adversely affecting survival. INTERPRETATION & CONCLUSIONS: Our results showed that lung cancer in Indians involved younger subjects and associated with poorer survival as compared to other ethnic population. Studies on large sample need to be done to evaluate risk factors in lung cancer patients.

Prevalence of chronic cough, chronic phlegm & associated factors in Mysore, Karnataka, India.

BACKGROUND & OBJECTIVES: Chronic cough and chronic phlegm are important indicators of respiratory morbidity, accelerated lung function decline, increased hospitalization and mortality. This study was planned to estimate the prevalence of chronic cough and phlegm in the absence of dyspneoa and wheezing and to study its associated factors in a representative population of Mysore district. METHODS: A cross-sectional survey was planned in a representative population of Mysore taluk. Eight villages were randomly selected based on the list of villages from census 2001. Trained field workers using the Burden of Obstructive Diseases questionnaire carried out a house-to-house survey. RESULTS: A total of 4333 adult subjects were enrolled in the study with 2333 males and 2000 females. The prevalence of chronic cough in the community was 2.5 per cent and that of chronic phlegm was 1.2 per cent. A significant association was observed between chronic cough and age, gender, occupation and smoking and chronic phlegm with age, gender, occupation, indoor animals and smoking. A multivariate analysis confirmed independent association of age, occupation and smoking for chronic cough and age and smoking for chronic phlegm. On sub-group analysis of males, heavy smokers had higher prevalence of chronic cough and chronic phlegm as compared to light smokers and non smokers. INTERPRETATION & CONCLUSIONS: The prevalence of chronic cough was 2.5 per cent and chronic phlegm was 1.2 per cent in the general population in Mysore which is lower than that observed in other studies. Heavy smoking was an important preventable risk factor identified in this study and efforts towards smoking cessation are crucial to achieve good respiratory health in the community.

Validation of a structured questionnaire for COPD and prevalence of COPD in rural area of Mysore: A pilot study.

BACKGROUND: The prevalence of chronic obstructive pulmonary disease (COPD) is increasing in India and there is a need to study the prevalence of COPD, particularly in the rural areas, which may be most affected due to their lifestyle. MATERIALS AND METHODS: FIRST STAGE: Validation of the questionnaire-105 consecutive patients underwent administration of the structured questionnaire and spirometry was used as a gold standard for the diagnosis of COPD. Second stage: Adults above 40 years (n = 900) in two villages of Mysore district were administered with the validated questionnaire, Knowledge and Attitude questionnaire and Fagerstorm questionnaire, to assess nicotine dependency. RESULTS: The questionnaire was found to have a sensitivity of 62.5% and specificity of 87.6% to diagnose COPD. Of the total 900 adults surveyed (Males: 453, Females: 447), the total prevalence of COPD was 7.1%. Males had a higher prevalence (11.1%) compared to females (4.5%). The prevalence of smoking was very high among men at 71.9% and all the women were nonsmokers. The prevalence of COPD was 14.7% in smokers, 19.3% had mild to moderate nicotine dependency and 12.8% were highly dependent. Of the women exposed to regular biomass fuels, the prevalence of COPD was 3.9%, which increased to 4.8% on addition of regular passive smoking. In smoking, male gender and age were significantly associated with COPD (P < 0.05). CONCLUSION: The structured questionnaire is a useful tool for the screening of COPD in field studies. Smoking and biomass fuel exposure are important risk factors for COPD.