Indian Guidelines on Nebulization Therapy.

Inhalational therapy, today, happens to be the mainstay of treatment in obstructive airway diseases (OADs), such as asthma, chronic obstructive pulmonary disease (COPD), and is also in the present, used in a variety of other pulmonary and even non-pulmonary disorders. Hand-held inhalation devices may often be difficult to use, particularly for children, elderly, debilitated or distressed patients. Nebulization therapy emerges as a good option in these cases besides being useful in the home care, emergency room and critical care settings. With so many advancements taking place in nebulizer technology; availability of a plethora of drug formulations for its use, and the widening scope of this therapy; medical practitioners, respiratory therapists, and other health care personnel face the challenge of choosing appropriate inhalation devices and drug formulations, besides their rational application and use in different clinical situations. Adequate maintenance of nebulizer equipment including their disinfection and storage are the other relevant issues requiring guidance. Injudicious and improper use of nebulizers and their poor maintenance can sometimes lead to serious health hazards, nosocomial infections, transmission of infection, and other adverse outcomes. Thus, it is imperative to have a proper national guideline on nebulization practices to bridge the knowledge gaps amongst various health care personnel involved in this practice. It will also serve as an educational and scientific resource for healthcare professionals, as well as promote future research by identifying neglected and ignored areas in this field. Such comprehensive guidelines on this subject have not been available in the country and the only available proper international guidelines were released in 1997 which have not been updated for a noticeably long period of over two decades, though many changes and advancements have taken place in this technology in the recent past. Much of nebulization practices in the present may not be evidence-based and even some of these, the way they are currently used, may be ineffective or even harmful. Recognizing the knowledge deficit and paucity of guidelines on the usage of nebulizers in various settings such as inpatient, out-patient, emergency room, critical care, and domiciliary use in India in a wide variety of indications to standardize nebulization practices and to address many other related issues; National College of Chest Physicians (India), commissioned a National task force consisting of eminent experts in the field of Pulmonary Medicine from different backgrounds and different parts of the country to review the available evidence from the medical literature on the scientific principles and clinical practices of nebulization therapy and to formulate evidence-based guidelines on it. The guideline is based on all possible literature that could be explored with the best available evidence and incorporating expert opinions. To support the guideline with high-quality evidence, a systematic search of the electronic databases was performed to identify the relevant studies, position papers, consensus reports, and recommendations published. Rating of the level of the quality of evidence and the strength of recommendation was done using the GRADE system. Six topics were identified, each given to one group of experts comprising of advisors, chairpersons, convenor and members, and such six groups (A-F) were formed and the consensus recommendations of each group was included as a section in the guidelines (Sections I to VI). The topics included were: A. Introduction, basic principles and technical aspects of nebulization, types of equipment, their choice, use, and maintenance B. Nebulization therapy in obstructive airway diseases C. Nebulization therapy in the intensive care unit D. Use of various drugs (other than bronchodilators and inhaled corticosteroids) by nebulized route and miscellaneous uses of nebulization therapy E. Domiciliary/Home/Maintenance nebulization therapy; public & health care workers education, and F. Nebulization therapy in COVID-19 pandemic and in patients of other contagious viral respiratory infections (included later considering the crisis created due to COVID-19 pandemic). Various issues in different sections have been discussed in the form of questions, followed by point-wise evidence statements based on the existing knowledge, and recommendations have been formulated.

Predictors of response to pulmonary rehabilitation in stable chronic obstructive pulmonary disease patients: A prospective cohort study.

Context: Pulmonary rehabilitation (PR) has become a standard of care in the management of chronic obstructive pulmonary disease (COPD). However, a significant proportion of the patients do not show benefit after the PR program. Aims: The study was planned to find different patient- and/or disease-related factors that may predict response to PR in stable COPD. Subjects and Methods: A total of 102 stable COPD patients were prospectively enrolled. Baseline evaluation and investigations, including spirometry, arterial blood gas analysis, and bone mineral density assessment, were done. Thereafter, all patients underwent an 8-week comprehensive outpatient PR program that consisted of exercise training, education, nutritional, and psychological counseling. The response to PR was dichotomously (yes/no) defined by the combined improvement in exercise tolerance (6-min walk distance [6MWD] +54 m) and quality of life (St. George's Respiratory Questionnaire [SGRQ] score - 4 points) measured before and after the program. Thereafter, different predefined factors were analyzed for their possible association with the PR response. Results: A total of 80 patients (78.4%) completed the PR program and were subjected for analysis. Out of them, 42 (52.5%) showed improvement in both 6MWD and SGRQ score (46 in 6MWD and 54 in SGRQ score). After application of multivariate logistic regression analysis, forced expiratory volume in 1 s <50% predicted (odds ratio [OR]: 2.9; 95% confidence interval [CI]: 1.1-8.3; P = 0.04) and osteoporosis (OR: 0.26; 95% CI: 0.13-0.53; P < 0.001) were found as independent factors predicting PR efficacy. Conclusions: Poor baseline lung function predicts a short-term improvement in exercise capacity and quality of life in COPD patients, whereas osteoporosis is a negative predictor of PR response. Active search for these factors may help in better patient selection, thus leading to improved outcome after PR.

Factors predicting treatment success in multi-drug resistant tuberculosis patients treated under programmatic conditions.

BACKGROUND: Treatment success in multi-drug resistant tuberculosis under programmatic conditions has been far from satisfactory. Knowledge of the factors predicting treatment outcome can guide us to take appropriate corrective measures for better results. However, there is a scarcity of data on these predictors in Indian patients. The present study was sought to evaluate association of different patient and disease specific factors with treatment outcome in MDR-TB patients. METHODS: It was a retrospective study that involved evaluation of data of MDR-TB patients who were started on Cat-IV treatment between January 2012 and December 2014. Medical records of 256 patients were scrutinized and necessary information on possible predicting factors like age, gender, body mass index, co-morbidities, previous TB treatment, blood investigations, treatment adherence, culture conversion time, etc. was retrieved. These factors were analyzed for their possible association with treatment outcome. RESULTS: Of the 256 patients, 132 (51.6%) achieved successful outcome after Cat-IV anti-TB regimen. On multivariate logistic regression analysis age (adjusted OR=0.95; 95% CI 0.91-0.98; p=0.01), serum albumin level (adjusted OR=3.71; 95% CI: 1.22-11.3; p=0.02) and treatment adherence (adjusted OR=4.52; 95% CI: 1.2-16.6; p=0.02) were independently associated with treatment success. Co-morbidities like diabetes and alcoholism and previous anti-TB treatment didn't affect the treatment end result significantly. CONCLUSION: The treatment outcome in MDR-TB has not significantly improved since the inception of DOTS-Plus strategy. Interventions to improve nutrition and treatment adherence might help to improve the success rate in MDR-TB treatment.

Evaluation of tuberculosis-associated chronic obstructive pulmonary disease at a tertiary care hospital: A case-control study.

CONTEXT: Irreversible airway obstruction is important sequelae of pulmonary tuberculosis (TB) that might contribute to a significant proportion of chronic obstructive pulmonary disease (COPD). India has the highest TB burden in the world. However, there are limited data on the prevalence and presentation of TB-associated COPD from this region. AIMS: This study aims to evaluate the prevalence of TB-associated COPD among COPD patients presenting to a tertiary care hospital. SETTINGS AND DESIGN: It was a case-control study conducted in a tertiary care hospital. SUBJECTS AND METHODS: Stable COPD patients presenting to chest OPD and an equal number of healthy controls were enrolled. COPD patients were subjected to detailed clinical evaluation and lung function test. History of pulmonary TB was evaluated from both groups through self-reporting and/or checking previous records. TB-associated COPD patients were identified and their prevalence and distinguishing features evaluated. RESULTS: Of 74 COPD patients, 24 (32.4%) had previous history of pulmonary TB. The odds of having a previous TB in COPD patients was 3.96 (95% confidence interval: 1.64-9.55; P = 0.002) as compared to controls. Patients with TB-associated COPD were younger (P = 0.02), had lesser pack-years of smoking (P = 0.027) but had more number of hospitalizations (P = 0.01). The airflow limitation was similar in both groups. CONCLUSIONS: TB-associated COPD constitutes a significant proportion of COPD patients. It is a distinct clinical entity with preponderance in young. It may be associated with frequent hospitalizations as compared to other COPD patients.

Guidelines for Diagnosis and Management of Bronchial Asthma: Joint Recommendations of National College of Chest Physicians (India) and Indian Chest Society.

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.

Treatment Outcome Among the Retreatment Tuberculosis (TB) Patients under RNTCP in Chandigarh, India.

BACKGROUND: 'RETREATMENT' for Tuberculosis (TB) has long been a neglected area in global TB control. While other components of the Stop TB Strategy have garnered appropriate focus and, increasingly, sufficient resources, issues related to the TB of patients previously treated for tuberculosis remain under examined and under-resourced. METHODS: A longitudinal study was designed and the patients registered under Revised National Tuberculosis Control Programme (RNTCP) category II from June 2010 to December 2011.Out of total 607 patients registered during this period under category II of RNTCP in Chandigarh (India), 545 consented to participate in the study. These were followed up to September 2012 till the completion of treatment. STATISTICAL ANALYSIS: The analysis was done by using SPPS-18 statistical software package. Chi- square test was used for testing association of different characteristics. RESULTS: Four Hundred Thirty (78.9%) of the patients had pulmonary TB and 115(21.1%) of the patients had extra pulmonary TB. In the study cohort of category II patients 264(48.4%) were relapse patients,167(30.6%) belonged to others category, 75(13.8%) were on treatment after default, 39(7.2%) were failure cases. The mean age of patients was 35.92 ± 15.42 (p = 0.928). Maximum patients belonged to age group of 25-34 years (25.3%). Seventy Three (13.4%) were Illiterate. In treatment after default group only 65.3% patients were cured. Maximum deaths 8% were seen in treatment after default group of patients. The overall default in the study was 5.9%. CONCLUSION: The findings of this study suggest that it is essential to monitor re-treatment patients with same vigour to reduce default and improve their treatment outcome.

Assessment of health-related quality of life in patients with pulmonary tuberculosis under programme conditions.

SETTING: Newly diagnosed pulmonary tuberculosis (PTB) patients starting treatment under the Revised National Tuberculosis Control Programme (RNTCP) in a North Indian city. OBJECTIVE: To quantify impairment in health-related quality of life (HRQoL) of PTB patients at the time of diagnosis and during treatment, and to assess the utility of these assessments as a measure of outcome under programme conditions. DESIGN: HRQoL was assessed using the Hindi version of the 26-item World Health Organization Quality of Life (WHOQOL-BREF) scale at the start and end of the intensive phase and at completion of treatment. Four domain scores-physical, psychological, social relationships and environment-were calculated and compared between groups, based on different patient and disease characteristics. Psychometric evaluation was conducted by assessing acceptability, validity and responsiveness of the questionnaire. RESULTS: A total of 2654 HRQoL assessments were performed among 1034 patients. Domain scores were generally better among men, urban residents, younger patients, patients with higher socio-economic status and those with less severe disease. The WHOQOL-BREF demonstrated good psychometric properties, and domain scores improved with treatment. Residual HRQoL impairment was noted in some patients even at treatment completion. CONCLUSION: HRQoL is impaired in patients with PTB, and improves rapidly and significantly with programme-based treatment. HRQoL assessment can be used as an adjunct outcome measure for patients treated by the RNTCP.

Contribution of medical colleges to tuberculosis control in India under the Revised National Tuberculosis Control Programme (RNTCP): lessons learnt & challenges ahead.

Medical college faculty, who are academicians are seldom directly involved in the implementation of national public health programmes. More than a decade ago for the first time in the global history of tuberculosis (TB) control, medical colleges of India were involved in the Revised National TB Control Programme (RNTCP) of Government of India (GOI). This report documents the unique and extraordinary course of events that led to the involvement of medical colleges in the RNTCP of GOI. It also reports the contributions made by the medical colleges to TB control in India. For more than a decade, medical colleges have been providing diagnostic services (Designated Microscopy Centres), treatment [Directly Observed Treatment (DOT) Centres] referral for treatment, recording and reporting data, carrying out advocacy for RNTCP and conducting operational research relevant to RNTCP. Medical colleges are contributing to diagnosis and treatment of human immunodeficiency virus (HIV)-TB co-infection and development of laboratory infrastructure for early diagnosis of multidrug-resistant and/or extensively drug-resistant TB (M/XDR-TB) and DOTS-Plus sites for treatment of MDR-TB cases. Overall, at a national level, medical colleges have contributed to 25 per cent of TB suspects referred for diagnosis; 23 per cent of 'new smear-positives' diagnosed; 7 per cent of DOT provision within medical college; and 86 per cent treatment success rate among new smear-positive patients. As the Programme widens its scope, future challenges include sustenance of this contribution and facilitating universal access to quality TB care; greater involvement in operational research relevant to the Programme needs; and better co-ordination mechanisms between district, state, zonal and national level to encourage their involvement.

Tuberculous lymphadenopathy: a multicentre operational study of 6-month thrice weekly directly observed treatment.

SETTING: Eight operational locations for the Revised National Tuberculosis Control Programme in six Indian states. OBJECTIVE: To assess the 6-month efficacy of an intermittent thrice-weekly directly observed treatment (DOT) regimen for tuberculous peripheral adenopathy and the need for prolongation of treatment to 9 months for non-resolution of lymphadenopathy. DESIGN: Patients aged >5 years with tuberculous lymphadenopathy were included in the study. Patients were evaluated for resolution at repeat visits following treatment. Those with poor resolution at 6 months were randomised to extended treatment up to 9 months or observation without additional treatment. RESULTS: Resolution of lymphadenopathy was observed at the end of 6 months in 517/551 (93.8%) patients. There was a significant difference in response among patients with and those without the presence of systemic symptoms. There was no association between treatment response and number, size, site, consistency and matting of lymphadenopathy. No differences in response were seen in the remaining 34 patients with or without extended treatment. CONCLUSION: The operational efficacy of 6-month thrice-weekly DOT for peripheral tubercular lymphadenopathy was satisfactory. There was no evidence of additional benefits of prolonging treatment to 9 months.

Tuberculosis lymphadenitis in a well managed case of sarcoidosis.

Differentiation between tuberculosis (TB) and sarcoidoisis is sometimes extremely difficult. Sequential occurrence of sarcoidosis and TB in the same patient is uncommon. We present the case of a young man, with a proven diagnosis of sarcoidosis who later developed TB after completion of treatment for sarcoidosis. A 32-year-old male patient presented with low-grade fever since two months. Physical examination revealed cervical lymphadenopathy. Initial fine needle aspiration cytology (FNAC) of the cervical lymph node was suggestive of granulomatous inflammation; the chest radiograph was normal. Repeat FNAC from the same lymph node was suggestive of reactive lymphoid hyperplasia. The patient was treated with antibiotics and followed-up. He again presented with persistence of fever and lymphadenopathy and blurring of vision. Ophthalmological examination revealed uveitis, possibly due to a granulomatous cause. His repeat Mantoux test again was non-reactive; serum angiotensin converting enzyme (ACE) levels were raised. This time an excision biopsy of the lymph node was done which revealed discrete, non-caseating, reticulin rich granulomatous inflammation suggestive of sarcoidosis. The patient was treated with oral prednisolone and imporved symptomatically. Subsequently, nearly nine months after completion of corticosteroid treatment, he presented with low-grade, intermittent fever and a lymph node enlargement in the right parotid region. FNAC from this lymph node showed caseating granulomatous inflammation and the stain for acid-fast bacilli was positive. He was treated with Category I DOTS under the Revised National Tuberculosis Control Programme and improved significantly. The present case highlights the need for further research into the aetiology of TB and sarcoidosis.

Endobronchial non-Hodgkin's lymphoma presenting as mass lesion.

A 40-year-old male presented with clinical and radiological manifestations of right lung atelectasis and post-obstructive pneumonia. Flexible bronchoscopy revealed gross narrowing of the right upper lobe bronchus and a smooth, white endobronchial mass completely occluding the right lower lobe bronchus. Endobronchial biopsy from the mass lesion yielded low grade B-cell non-Hodgkin's lymphoma. This is one of the rarest presentation of non-Hodgkin's lymphoma.

Concurrent infection of pneumocystis pneumonia and pulmonary tuberculosis in an HIV-seronegative patient.

Co-infection with Pneumocystis jirovecii and Mycobacterium tuberculosis is rarely reported in patients without human immunodeficiency virus (HIV) infection. We describe the case of a 33-year-old HIV-negative female patient who was on long-term oral corticosteroids for rheumatoid arthritis and admitted with for respiratory distress and diffuse infiltrative pneumopathy in whom concurrent infection with Mycobacterium tuberculosis and Pneumocystis jiroveci was confirmed by bronchoalveolar lavage (BAL) fluid examination.

Combined effect of GSTM1, GSTT1 and GSTP1 polymorphisms on histological subtypes of lung cancer.

Genetic polymorphisms are natural genetic variations in the gene sequence that occur at a frequency of >1% in the population. This genetic variability (polymorphisms) can be a factor in cancer risk. The functional polymorphisms in GST genes play an important role in susceptibility to lung cancer. In our previous study, we reported that the combination of certain genotypes of GSTM1, GSTT1 and CYP1A1 is associated with lung cancer. The study has been extended to investigate the potential role of polymorphism in GSTP1 alone or in combination with the status of GSTM1 and GSTT1 genes in the likelihood of development of lung cancer. A total of 302 subjects (151 cases and 151 controls) were evaluated. Using a case-control design, individuals were genotyped for GSTs using multiplex polymerase chain reaction and restriction fragment length polymorphism techniques. The data obtained were analyzed using multiple logistic regression. The combined 'at risk' genotypes of GSTM1 null and GSTT1 null in comparison with 'wild-type' genotypes seems to be associated with a greater risk of lung cancer, but the results are not significant (odds ratio (OR) 2.0, 95% confidence interval (CI) 0.68-5.96) and for squamous cell carcinoma (SqCC) it was 1.6-fold (OR 1.6, 95% CI 0.49-5.68). In summary, our case-control study of lung cancer revealed that the effect of these polymorphisms is not very marked for different genotypic combinations of GSTP1, GSTM1 and GSTT1 in the context of developing lung cancer in a north Indian population. However, the increased risk was limited to SqCC, and was not found for other histological subtypes. Further analyses on this topic are needed.

Treatment outcomes of patients placed on treatment under directly observed therapy short-course (dots).

BACKGROUND: Tuberculosis continues to be a pressing health problem in India. The Revised National Tuberculosis Programme (RNTCP), an application of Directly Observed Treatment Short-course (DOTS) in India, launched in 1997 needs continuous evaluation. OBJECTIVE: To study the outcomes of treatment among the patients put on DOTS under RNTCP in Chandigarh, UT. MATERIAL #ENTITYSTARTX00026; METHODS: A Longitudinal study was conducted during 2004-2005 in 13 Microscopic centres (MC's) spread over 2 Tuberculosis Units (TU's) under District Tuberculosis Centre (DTC) in Union Territory (UT), Chandigarh. A sample of 265 respondents, selected by two-stage stratified random sampling technique, was recruited in the study cohort. Data analysis was done using SPSS-10 statistical software package. RESULTS: For Category I and Category II patients, the Success rate was 98.6% and 90.4% respectively. The overall default rate was 1.1% and failure rate was 2.6%. For re-treatment cases, failure rate was higher i.e. 5.8%. The sputum conversion rate among the new smear positive cases was 93.8% at 3 months of treatment. For the re-treatment cases, spu-tum conversion rate at 3 months was 94.1%. CONCLUSION: The study concludes that RNTCP is running successfully in UT Chandigarh, having high success rate and low default rate. The reasons for high failure rate should be explored in depth.

Effects of cyclin D1 (CCND1) polymorphism on susceptibility to lung cancer in a North Indian population.

Cyclin D1 is involved in normal regulation of the cell cycle and plays an important role in the transition from G1 to S phase of the cell cycle. The CCND1 gene has a G-->A polymorphism in exon 4 that increases the frequency of alternate splicing. We analyzed the potential role of CCND1 gene polymorphisms in lung cancer patients (n = 151) and in a matched control population (n = 151). DNA was isolated from blood samples, and exon 4 of CCND1 was amplified by polymerase chain reaction. After digestion with MspI, common CCND1 polymorphic alleles were analyzed by means of agarose gel electrophoresis. The data obtained were analyzed using multiple logistic regression. After adjustment for age, sex, and smoking status, the AG genotype was associated with an increased risk for overall lung cancer (odds ratio OR = 1.7, 95% confidence interval CI = 0.92-3.14). No association was found between AA genotype and risk of lung cancer. In smokers, the combined AG+AA genotypes of CCND1 were found to be significant (OR = 1.9, 95% CI = 1.03-3.71, P = 0.03). No positive association was found between CCND1 genotypes in nonsmokers. The results suggest that the CCND1 A870G gene polymorphisms may increase the risk of lung cancer in smokers from north India.

Psychotherapy improves compliance with tuberculosis treatment.

BACKGROUND: Low treatment completion rate in tuberculosis (TB) patients is a major concern. Physicians have always been striving for better treatment adherence in such patients. The present study is one such attempt in this direction. OBJECTIVES: The study was aimed to evaluate the role of behavior modification by psychotherapy in improving compliance with short-course anti-TB chemotherapy in India. METHODS: It was a prospective controlled trial involving patients with confirmed pulmonary and extrapulmonary TB enrolled in the National Tuberculosis Program. The intervention group underwent pretreatment psychological assessment followed by regular psychotherapy sessions. RESULTS: The intervention group had a demographic profile comparable to that of the control group. The patients were mostly from low- and middle-income backgrounds from urban and semi-urban areas. They consistently showed poor knowledge about the nature of the disease, low motivation, and had considerable apprehensions. Following the sessions, the intervention group showed improved compliance compared with the control group, reflected in significantly higher treatment completion and cure rates. CONCLUSIONS: The study suggests that psychological intervention is effective in improving compliance with anti-TB treatment, and may reduce the incidence of treatment failure, relapse and drug resistance.

Subungual erythema in lymph node tuberculosis with erythema nodosum.

We encountered a case of tuberculous lymphadenitis with erythema nodosum presenting with an unusual manifestation as subungual erythema in all the digits. Relevant literature and the possible explanation for the subungual erythema have been discussed.

Cervico-mediastinal lymphadenopathy as a paradoxical response to chemotherapy in pulmonary tuberculosis. A case report.

We report a case of pulmonary tuberculosis who developed tuberculous mediastinal and later cervical lymphadenopathy while on antituberculous chemotherapy. She responded to the addition of oral corticosteroids to her regimen. The relevant literature regarding the pathogenesis, varied manifestations and the clinical importance of recognising a paradoxical response is discussed.

Tuberculosis of the parotid gland.

Tuberculosis of the parotid gland is a rare entity. Only about a hundred cases have been reported till date, mostly from parotidectomy specimens. The present case was diagnosed by fine needle aspiration and treated successfully by short-course antitubercular chemotherapy. An early diagnosis can avoid parotidectomy, which can be a hazardous procedure in a medically treatable condition.