National Registry of Interstitial Lung Disease from Pakistan.

Introduction Interstitial lung disease (ILD) is a heterogeneous group of over 200 parenchymal lung diseases with a myriad of etiologies. Interstitial lung disease registries from around the world show varying prevalence and incidence of these diseases. The aim of this study was to determine the epidemiology and characteristics of ILD in Pakistan. Methods This web-based registry, which is the first multicenter registry of ILD from Pakistan, recruited patients from 10 centers of five major cities between January 2016 and March 2019. Results A total of 744 patients were enrolled in the registry. The five most frequent ILDs were idiopathic pulmonary fibrosis (IPF) 34.4%, hypersensitivity pneumonitis (HP) - 17.7%, idiopathic nonspecific interstitial pneumonitis (iNSIP) - 16.8%, connective tissue disease-associated ILD (CTD-ILD) - 16.3%, and sarcoidosis - 9.1%. Conclusion Idiopathic pulmonary fibrosis is the most prevalent ILD in Pakistan, followed by HP and iNSIP. An ongoing prospective registry with longitudinal follow-up will help us further elaborate on the clinical characteristics, treatment, and survival outcome of patients with ILD.

Diagnostic Accuracy of Xpert MTB/RIF in Sputum Smear-Negative Pulmonary Tuberculosis.

Introduction Tuberculosis is a major health problem in Pakistan. The prevalence of pulmonary as well as extrapulmonary tuberculosis is quite high. Tuberculin skin test, radiological imaging, and sputum smear microscopy have limitations in the diagnosis of tuberculosis. Xpert MTB/RIF was recently approved for the diagnosis of pulmonary tuberculosis and has shown promising results. The aim of this study was to determine the diagnostic accuracy of Xpert MTB/RIF in sputum smear-negative pulmonary tuberculosis using acid-fast bacilli (AFB) culture as the gold standard. Materials and methods This cross-sectional study was conducted at Iqbal Yad Chest Clinic and Nazimabad Chest Clinic of Ojha Institute of Chest Diseases, Dow University of Health Sciences. Patients of either gender aged 18-65 years suspected to have pulmonary tuberculosis with at least two sputum samples negative for AFB underwent Xpert MTB/RIF testing. Early morning sputum samples were obtained and sent for AFB smear microscopy, Xpert testing and also for culture analysis. Results Mean age of the patients was 37.48 ±17.49 years. There were 84 (37.3%) females and 141 (62.7%) males. Positive findings on Xpert MTB/RIF were found in 147 (65.3%) patients whereas AFB culture showed positive findings in 174 (77.3%) patients. Sensitivity, specificity, positive predicted value, negative predicted value and overall diagnostic accuracy of Xpert MTB/RIF was found to be 84.48%, 100%, 100%, 65.38%, and 88%, respectively. Conclusion Xpert MTB/RIF has high sensitivity, specificity, and diagnostic accuracy in diagnosis of sputum smear-negative cases of pulmonary tuberculosis.

Six-minute walk test performance in healthy adult Pakistani volunteers.

OBJECTIVE: To determine the six-minute walking distance (6MWD) for healthy Pakistanis, identify factors affecting 6MWD, compare published equations with the local data and derive an equation. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Two medical institutes of Karachi, from January to May 2011. METHODOLOGY: Subjects between 15 and 65 years were prospectively enrolled after screening. A standardized 6MWT was administered. SpO2, HR, BP and dyspnoea scores were determined pre- and post-test. RESULTS: Two hundred and eleven (71%) men and 85 (29%) women participated. Mean 6MWD was 469.88 ± 101.24 m: men walked 502.35 ± 92.21 m and women walked 389.28 ± 74.29 m. On univariate analysis, gender, height, weight and age showed a significant relationship with the 6MWD. Gender and age were identified as independent factors in multiple regression analysis, and together explained 33% of the variance. The gender-specific prediction equations were: 6MWD (m) for men = 164.08 + (78.06*1) - (1.90*age in years) + (1.95*height in cms) 6MWD (m) for women = 164.08 - (1.90*age in years) + (1.95*height in cms). CONCLUSION: 6MWDs among the volunteer subjects were shorter than predicted by reference equations in literature. Height, gender and weight combined explained 33% of the variance. The moderate over-estimation of the 6MWD in Pakistani subject. The proposed equation gives predicted (mean) 6MWDs for adult Pakistani naïve to the test when employing standardized protocol.

Drug resistance pattern in multidrug resistance pulmonary tuberculosis patients.

OBJECTIVE: To evaluate the frequency of drug resistance profiles of multidrug resistant tuberculosis (MDR-TB) isolates of pulmonary tuberculosis patients, against both the first and the second line drugs. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: The multidrug resistant tuberculosis (MDR-TB) ward of Ojha Institute of Chest Diseases (OICD), Karachi, from 1996 to 2006. METHODOLOGY: Culture proven MDR-TB cases (resistant to both isoniazid and Rifampicin) were retrospectively reviewed. Susceptibility testing was performed at the clinical laboratory of the Aga Khan University. Sensitivity against both first and second line anti-tuberculosis drugs was done. Susceptibility testing was performed using Agar proportion method on enriched middle brook 7H10 medium (BBL) for Rifampicin, Isoniazid, Streptomycin, Ethambutol, Ethionamide, Capreomycin and Ciprofloxacin. Pyrazinamide sensitivity was carried out using the BACTEC 7H12 medium. During the study period MTB H37Rv was used as control. RESULTS: Out of total 577 patients, all were resistant to both Rifampicin and Isoniazid (INH). 56.5% isolates were resistant to all five first line drugs. Resistances against other first line drugs was 76.60% for Pyrazinamide, 73% for Ethambutol and 68.11% for Streptomycin. Five hundred and ten (88%) cases were MDR plus resistant to one more first line drug. Forty (07%) isolates were MDR plus Quinolone-resistant. They were sensitive to Capreomycin but sensitivity against Amikacin and Kanamycin were not tested. CONCLUSION: There were high resistance rates in MDR-TB to remaining first line and second line drugs. Continuous monitoring of drug resistance pattern especially of MDR isolates and treatment in specialized centers is a crucial need for future TB control in Pakistan.

Variables predictive of outcome in patients with acute hypercapneic respiratory failure treated with noninvasive ventilation.

OBJECTIVE: To assess results with NIV in acute hypercapneic respiratory failure and to identify outcome predictors. METHODS: This was a retrospective observational study on consecutive patients presenting with acute type II respiratory failure and meeting criteria for NIV use over a 5 year period. Patients presenting with haemodynamic instability, inability to protect their airway, malignant arrhythmias and recent oesophageal surgery were excluded. Univariate and Multivariate regression analysis was used to determine the impact on survival. A p value of < 0.05 was considered statistically significant. Software used was SPSS 14. RESULTS: Total numbers of patients included were 119; 52.9% were males. Mean age was 63.4 +/- 11.9 years. Overall Survival to discharge rate was 76.5%, intubation rate was 12.6% and mean length of stay was 11.4 +/- 10.9 days. Statistically significant improvements were observed in the pH and PaCO2 at 24 hours and 48 hours compared to baseline (7.28 v/s 7.37, p < 0.001; 74.2 v/s 65, p < 0.001). On multivariate regression analysis, sepsis at admission predicted mortality (adjusted Odds ratio 26.4; 95% CI 2.3, 304, p < 0.009). A serum HCO3 > 35 Meq/L (adjusted Odds ratio 0.9; 95% CI 0.83, 0.98, p < 0.015) identified those less at risk for intubation. CONCLUSION: NIV was found to be both safe and effective in the management of acute hypercapneic respiratory failure. Sepsis and serum HCO3 at admission identified patients having poor outcomes.

Treatment outcome of multi-drug resistant tuberculosis in a tertiary care hospital in Karachi.

OBJECTIVE: To assess the outcomes of pulmonary multidrug-resistant tuberculosis (MDR-TB) patients treated at Ojha Institute of Chest Diseases (OICD), a reference hospital for TB in Karachi, Pakistan. METHODS: Clinical study for the period 1996-2006, with follow-up until June 2007 was performed. All the culture and sensitivity proven cases of MDR pulmonary TB were initially admitted for 3-6 months till the sputum converted negative. Treatment regimen was decided on individual basis, and included 4-6 drugs. Supervised treatment was given to all patients during the hospitalization. After discharge from the hospital, patients were followed at monthly interval at the outpatient department of OICD for 18 months total. RESULTS: Five hundred and seventy nine adult patients (59.93% male) with mean age of 32.44 +/- 12.63 years were studied. All patients had a history of treatment with first line anti-tuberculosis drugs. Treatment was successful in 227 (39.2%). The mortality rate was 27(4.6%) during hospitalization. During admission 83(14.3%) left treatment and 239 (41.2%) were lost to follow-up during treatment. Treatment failure was observed in three patients. CONCLUSION: The treatment success rate in this study is satisfactory but high default rate is a challenge in the management of MDR tuberculosis.

Magnitude of initial default in pulmonary tuberculosis.

OBJECTIVE: To assess the magnitude and reasons of initial default in pulmonary tuberculosis patients, diagnosed at Nazimabad Chest Clinic, Karachi. METHODS: This prospective study was conducted over five months from 1st December 2007 to 30th April 2008. Suspected tuberculosis patients were prescribed sputum AFB (Acid Fast Bacilli) smears for three samples. This study included the smear positive patients who did not collect their report and were therefore defaulters for initiation of anti-tuberculosis treatment. These patients were contacted on phone, reasons of defaults were enquired and they were offered free treatment. RESULTS: In the study period, out of 869 tuberculosis suspects, 224 were diagnosed as smear positive pulmonary tuberculosis. Of these 224, one hundred and sixty-two got themselves registered for treatment. The remaining 62/224 (27.67%) were initial defaulters. On telephonic contact, 55 (88.70%) were traceable while 07/62 (11.29%) were Untraceable-defaulters. Twenty-four patients (38.70%) reported to the clinic and were registered for treatment. The most common reason for default was 'dissatisfaction with services at the clinic'. CONCLUSION: A high initial default for initiating Anti-Tuberculosis Therapy is a serious issue that needs to be addressed.

Primary drug resistance against Mycobacterium tuberculosis in Karachi.

OBJECTIVE: To evaluate the primary drug resistance of new culture positive cases of pulmonary tuberculosis in Karachi. METHODS: All new suspected pulmonary tuberculosis patients were recruited initially. They were instructed to produce three-sputum samples for smear examination and on one of the specimen's culture was applied. Bronchoscopy and bronchial wash was done in patients who were not expectorating. Bronchial wash was then applied for both smear and culture for Mycobacterium tuberculosis. RESULTS: Out of 79 cases recruited initially, 52 were able to produce sputum while bronchoscopy was performed in the remaining. AFB direct smear was positive in 32/52 sputum and 12/27 bronchial wash samples. Later, 02 sputums and 04 bronchial washes became culture positive which were initially smear negative. All cultures were of Mycobacterium tuberculosis species. These fifty culture positive cases were then included in the final analysis. Pyrazinamide was the most sensitive drug i.e. 49 isolates (98%). The resistance pattern is as follows: Streptomycin 13(26%), Isoniazid 08 (16%), Ethambutol 08 (16%), Rifampicin 04 (08%) and Pyrazinamide one (02%). Multi-Drug Resistant tuberculosis was observed in 02 (04%) patients. CONCLUSION: In this small study, the high prevalence of primary resistance against streptomycin, INH and Ethambutol raises an urgent need of a proper nationwide survey to evaluate the true picture of primary resistance.

New drugs in resistant tuberculosis.

The World Health Organization estimates that up to 50 million persons worldwide may be infected with drug resistant strains of TB. The fatality rate of MDR-TB is 20-80%. Drug resistant tuberculosis cases are on the rise in Pakistan. The reasons for this menace are multiple including improper prescription, compliance and over the counter sale of anti-TB drugs. The treatment cost of drug-resistant TB is high, both to the individual patient and society. This article is written to create awareness about the available second line drugs and those in the pipeline. Considering the fact that resistant tuberculosis is difficult to manage, it is suggested that these drugs should only be used after consultation with a physician experienced in the treatment of drug resistant TB. The most frequent mistake made by treating physicians is addition of one drug in the failing regimen. At present, 27 potential anti-TB drugs are at various stages of development. The aim is that by 2010 at least one of these molecules completes the journey and should come in the market.