Impact of Using Global Lung Initiative Race-neutral Equations for Chronic Respiratory Disease in Western India.

The Global Lung Initiative (GLI) race-neutral equations are considered to be race agnostic, using inverse probability weight, and have lower limits of normality (LLN) different from the GLI mixed equations. In this observational study, we analyzed the impact of using GLI equations to interpret spirometry of 1,169 patients with chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), COPD suspects, small airway obstruction, posttubercular lung disease, and preserved ratio with impaired spirometry (PRISm) (46% females, average age 46 years). Predicted normal and the LLN using GLI equations were significantly higher than those using Indian equations. The GLI race-neutral equations changed the category in 35.17% of males and 42.64% of females compared to Indian equations. The GLI mixed equations categorized a greater percentage of patients to have a mixed ventilatory pattern compared to the GLI race-neutral equations. There was a significant change in the grading of the severity of COPD using Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages based on the percentage of predicted values of FEV1. Although GLI race-neutral equations have greater concordance with Indian equations than GLI Mixed equations, these substantially overdiagnose abnormal ventilatory patterns on spirometry in adult Indians in western India with chronic respiratory disease. A substantial number of patients with normal or obstructive patterns on spirometry are recategorized to have mixed or restrictive patterns. The use of GLI race-neutral equations increases the severity of airflow limitation in COPD patients. GLI race-neutral predictions for FEV1 result in substantially fewer patients demonstrating postbronchodilator responsiveness (PBDR).

Biomarkers in severe asthma: Identifying the treatable trait.

Asthma is a chronic condition of bronchial hyper-reactivity associated with inflammation ranges from mild to severe form. It affects 1 - 18% of the population globally and it is estimated that > 300million people in the world have asthma. Of this 5 - 10% have severe asthma. while the proportion of patients suffering from severe are smaller, the morbidity and mortality are higher in this group. With the advances in our understanding of the pathophysiology of asthma there is a need to understand the role of various biomarkers. We live in an era of precision medicine and today there is a clear unmet need to understand targeted therapies. This review aims to raise awareness to the available biomarkers used in clinical practice in India and their role in predicting response to targeted therapies.

Hemoptysis after COVID: Pulmonary artery pseudoaneurysm treated with endovascular coiling.

Pulmonary artery pseudoaneurysms are a rare but life-threatening cause of hemoptysis. These are saccular dilatations of the pulmonary artery which do not involve all the three layers of the vessel and are prone to rupture. PAPAs are most commonly associated with infections but may also be caused by vasculitis, lung fibrosis, pulmonary hypertension and a multitude of other causes. CT pulmonary angiography is the diagnostic modality of choice allowing delineation of the PAPA, underlying cause and allowing planning of further management. Although treating the underlying cause is an important part of management, endovascular intervention is required in cases with hemoptysis. Long COVID is an entity that is still under evaluation. It has multisystem involvement. We describe the case of a 30-year-old teacher with hemoptysis after COVID who was diagnosed with a PAPA of segmental branch of left upper lobar pulmonary artery and treated with endovascular embolization with coils and glue. His hemoptysis has stopped since then. He also had pulmonary fibrosis and growth of multidrug resistant Klebsiella pneumoniae in sputum. These were treated medically and he has resumed his work as a teacher.

Platypnea-orthodeoxia Syndrome (POS) in Moderate COVID-19: An Uncommonly Common Bedside Sign?

Platypnoea-Orthodeoxia syndrome (POS) is the presence of postural hypoxaemia along with breathlessness in recumbent position. It is an uncommon syndrome with elusive pathophysiologic mechanisms. We observed POS in patients of moderate COVID-19 who required hospital admission to our indoor facility and oxygen supplementation when saturation was documented in sitting and supine positions for evaluation of platypnea. MATERIALS AND METHODS: We conducted an observational, cross sectional, retrospective analysis of pulse oximetry readings of patients with stage 2 COVID-19 admitted in ward during the period from 15th May 2020 to 30th May 2020. The difference in the peripheral oxygen saturation in sitting and supine positions, documented as a routine standard of care, especially in patients with platypnea, was calculated and demographic details and co-morbidities were noted from indoor record forms. RESULTS: Of the 53 patients of stage 2 COVID-19 who were included in the study, 15 (28%) had platypnoea-orthodeoxia syndrome at the time of presentation and 18(33.9%) patients with platypnoea had ≥ 3% desaturation in sitting position as compared to supine position. Rest of the 20 (37.7%) patients had neither platypnoea nor orthodeoxia. All the patients presenting with platypnoea-orthodeoxia required oxygen therapy during the course of treatment. Amongst the 33 patients who were hypoxic and required oxygen supplementation, 15 patients (45.4%) had oxygen saturation of ≥94% in the supine position at presentation. CONCLUSION: Platypnoea-orthodeoxia syndrome is common in patients with stage 2 COVID 19 infection who require oxygen therapy. POS can be easily documented by using pulse oximeter without the need of any specialised equipment. Hence, we propose that documentation of POS at the time of admission in primary health care or resource depleted settings would help in successful triage of the patients needing oxygen therapy. We also propose that oxygen saturation in sitting position be documented as far as possible. Further clinical studies are necessary to validate this observation.

Nasal Airway Resistance and Latent Lower Airway Involvement in Allergic Rhinitis.

INTRODUCTION: Allergic rhinitis (AR) and asthma are closely linked atopic conditions, often termed as one airway one disease. Nasal airflow obstruction is a cardinal symptom of AR and objective assessment of resistance to nasal airflow in rhinitis can be measured by active anterior rhinomanometry. This study was aimed at correlating the degree of resistance to nasal airflow (NAR) with the clinical severity of allergic rhinitis. In addition, it aimed at determining the proportion of patients with latent lower airway involvement in AR and studying the impact of ARIA severity grade and NAR on this value. MATERIALS AND METHODS: A prospective prevalence study was conducted wherein 32 patients diagnosed with allergic rhinitis underwent determination of nasal airway resistance by active anterior rhinomanometry and lung function evaluation by spirometry. If spirometry was normal; histamine challenge test was performed to check for bronchial hyper-reactivity. RESULTS: 94% of patients with moderate- severe allergic rhinitis had significantly elevated nasal airway resistance compared to 56% of patients with mild rhinitis. (p=0.014). 71.9% of patients with allergic rhinitis but no symptoms of asthma had bronchial hyper-reactivity with a positive histamine challenge or airflow obstruction on lung functions. 87.5% patients with significantly elevated nasal airway resistance compared to 25% with lower values had lower airway involvement. (p=0.001). 94% of patients with moderate - severe rhinitis and 83% of patients with persistent rhinitis compared to 50% patients with mild and 44% with intermittent symptoms had lower airways involved. (p<0.05). CONCLUSION: Significantly greater proportion of patients with moderate-severe and persistent allergic rhinitis had elevated nasal airway resistance values. 72% patients with allergic rhinitis had lower airway involvement despite having no symptoms of asthma, prevalence being greater in patients with severe and persistent disease. Proportion of patients with lower airway hyper-responsiveness is significantly higher among patients with raised nasal airway resistance as determined by rhinomanometry. This study thus concludes that measurement of nasal airway resistance determined by active anterior rhinomanometry is a good objective tool to measure severity of nasal obstruction in allergic rhinitis with good correlation with the ARIA clinical severity grade .It may also be a promising tool to identify allergic rhinitis patients who are at a higher risk of having latent lower airway involvement.

Association of Environmental Factors, Prevalence of Asthma and Respiratory Morbidity in Mumbai: Need of a Public Health Policy.

OBJECTIVE: To study the association between environmental factors, prevalence of asthma and respiratory morbidity in relation to air quality levels in a mega city. To study modifiable environmental factors in people with diagnosed asthma and increased respiratory morbidity. METHODS: Cross sectional survey of population (N-3233) from 6 localities near air quality stations was done to study prevalence of asthma and respiratory morbidity (n-1006) followed by case control study of environmental factors by air sampling to study biological contamination. RESULTS: Univariate analysis was performed to study effect of various risk factors. Respiratory morbidity was significantly high in areas with high SPM levels. Odd's ratio was 10.3 for wheezing, 9.16 for cough, and 12.6 for breathlessness. Presence of biological contamination of air [bacterial spores] was associated with respiratory morbidity with odds ratio of 2.2 in areas with open drainage system. Pigeon droppings were found to be the source of fungal spores and associated with respiratory symptoms with odds ratio of 1.8. CONCLUSIONS: Respiratory morbidity significantly rises in areas with high particulate matter levels and biological contamination of air. Identification of environmental risk factors in different localities will be useful for undertaking specific mitigation measures at local level as a public health measure.

Disseminated cryptococcosis with caverno-oesophageal fistula in a case of idiopathic CD4+ T-lymphocytopenia.

Idiopathic CD4+ T-Lymphocytopenia is a rare immunodeficiency disorder characterised by significantly low absolute CD4 lymphocytes in absence of any viral infections. We present a case of Disseminated Cryptococcosis with Caverno- Oesophageal Fistula in a case of Idiopathic CD4+ T-Lymphocytopenia. 29 year old lady was referred to Institute in view of lung mass not responding to anti-TB treatment. Subsequently patient had developed headache. Radiological evaluation showed presence of ring enhancing lesion in the occipital region. On evaluation with Fibre-optic bronchoscopy, there was no evidence of malignancy or tuberculosis. Sputum showed presence and growth of Cryptococcus neoformans. Patient's investigations were negative for virus infection, with normal immunoglobulin levels. Her CD4 counts were 129 cells/mm3. Patient was treated with injectable antifungals. Patient developed a Caverno-oesophageal fistula which was confirmed on endoscopy and radiology. Patient was managed with percutaneous jejunal feeding (PEJ). Patient improved symptomatically with CD4 count of 475 cells/mm3.

Serial lobar lung lavage in pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare disease with worldwide distribution and an estimated incidence of 0.36 cases per million. We report a case of a PAP coexisting with Pneumocystis jiroveci pneumonia and Mycobacterium tuberculosis infection. The patient was treated with serial lobar lung lavages, GM-CSF, cotrimoxazole, and antituberculosis drugs. His PaO2 on room air improved from 45.7 to 63.8 torr and pulmonary functions normalized (FVC 81.2%, FEV1 95.3%, FEV1/FVC 91.8). A high-resolution computed tomography scan of the thorax showed clearing of both lower lobes. Whole-lung lavage is used in the treatment of PAP, but it may worsen the hypoxemia and lead to hemodynamic instability during the procedure. To the best of our knowledge, there are no reports of bronchoscopic serial lobar lung lavages in cases of PAP performed in India. This method can be performed in bronchoscopic suites having general anesthesia facilities without the requirement of special gadgets.

Mycobacterium tuberculosis triggers autoimmunity?

Mycobacterial infections are known to induce the development of autoantibodies. This study was therefore carried out in endemic areas to look for the prevalence of autoantibodies in pulmonary and extra pulmonary tuberculosis, with and without rheumatological symptoms suggesting a possible role of mycobacterial infection triggering autoimmunity. The results reveal that there is a need for further studies to be carried out in relation to possible autoimmune phenomenon linked with Mycobacterium tuberculosis infections. Tuberculosis patients should ideally be screened for the presence of various autoantibodies, particularly for a detailed study on anti-nuclear antibody (ANA) specificities. Their significance has to be deciphered to understand the role of these background autoantibodies produced. It is important to screen all tuberculosis patients for autoantibody profile and should be followed up after the treatment for any flaring up of autoimmune related symptoms.

Incremental yield in sputum smear positivity by examining a second early morning sputum specimen in follow-up patients on DOTS: 7 year analysis of RNTCP laboratory register.

BACKGROUND: Patients receiving DOTS undergo periodic follow-up sputum examination, which aids in monitoring response to treatment. Continued or new smear positivity at follow up examination entails extension of intensive phase or change in treatment category and the need for culture and drug susceptibility test. SETTING: Tuberculosis microscopy centre at a tertiary care teaching hospital, Mumbai, India. OBJECTIVE: To determine the incremental yield in sputum smear positivity by examining a second early morning sputum specimen in follow-up patients on DOTS. DESIGN: Retrospective analysis of follow up sputum microscopy results recorded in tuberculosis laboratory register for the period 2002-2008. RESULTS: During the study period, 5015 follow-up patients submitted two early morning sputum specimens, of which 501(9.99%) patients were detected to be smear-positive. Out of smear positive patients under study, 324 patients had both specimens positive, 79 patients had only first specimen positive and 98 patients had only second specimen positive. The incremental yield was 1.95% of total and 19.5% of smear positives. CONCLUSION: Discordant smears were present in nearly a third of patients detected smear positive during follow-up. More than half of these patients were detected only by examining second specimen. The incremental yield by examining the second early morning specimen was 1.95% of total and 19.5% of smear positive specimens. It is important to detect each possible smear positive follow-up patient as they are likely to benefit from altered treatment. The inclusion of a second early morning sputum specimen examination is essential to maximize their detection.

Incidence of silicosis in flourmill workers.

BACKGROUND: Silicosis is an ancient occupational illness reported in silica mill workers, agate stone workers, slate pen workers and mining industry. However its association in flour mill workers has not been established. AIMS: To study the incidence of silicosis and respiratory morbidity in flour mill workers. SETTINGS AND DESIGN: A prospective study of 56 flour mill workers working with open silica grinding stones was undertaken. MATERIALS AND METHODS: 56 flour mill workers who volunteered following information regarding the study purpose were recruited from the community. Detailed clinical and occupational history, lung functions, chest x-ray, and high resolution computed tomography (HRCT) were done. Diagnosis was made on the basis of radiological findings. STATISTICAL ANALYSIS: Data analysis was done with the help of the statistical package for social sciences software. The Chi-square test was used for determining the relationship between qualitative data and descriptive statistics was used where required. RESULTS: 93% had respiratory symptoms that included cough (66.1%), dyspnea (75%), chest pain (17.1%), and rhinorrhea (46.4%). Radiological abnormalities were noted in chest X-ray (60.7%) and HRCT (81.48%). A significant correlation was seen between duration of exposure and HRCT abnormalities. Lung functions revealed obstruction in 28.5% subjects, restriction in 19%, mixed ventilatory defects in 21.4%, while 18.9% had a reduced diffusion capacity. CONCLUSION: Incidence of silicosis in our study on flour mill workers working with silica containing grinding stones was 30.4%. They had high respiratory morbidity (93%) cough and dyspnea being predominant symptoms. Duration of exposure correlates with radiological findings and increased incidence of silicosis.

Bronchoscopy in pulmonary hydatidosis: retrospective analysis.

The diagnosis of unruptured pulmonary hydatidosis is based on classical radiologic features. However, ruptured or complicated hydatid cysts alter the radiologic signs and lead to delayed or incorrect diagnosis. The role of flexible bronchoscopy was assessed as a diagnostic tool in the evaluation in such cases. Between 2002 and 2008, 14 patients (7 female, 7 male), aged between 18 and 55 years, with a mean age of 36 years, were evaluated for pulmonary hydatidosis. Clinical history, radiologic findings, and other investigations of the patients were reviewed retrospectively at a tertiary referral center. All 14 patients were symptomatic, with cough, hemoptysis, and chest pain being the most common symptoms. Seven patients had right lung involvement, whereas 6 patients had left-sided predilection, and the remainder presented with pleural disease. At flexible bronchoscopy, white glistening membrane could be observed in 9 patients, whereas cytologic evaluation of bronchial washing did not show cuticular particles, degenerated scoleces, or hooklets in any of the cases. Twelve patients underwent uneventful surgical intervention. Surgical specimens showed 2 unruptured pulmonary hydatid cysts (uncomplicated), 1 pleural hydatid, and 9 ruptured pulmonary hydatid cysts. Of the 9 ruptured hydatid cyst cases, evidence of fungal (aspergillus) colonization, bacterial infection, and coexistent tuberculous granuloma was reported in 2 cases each. Bronchoscopy is an important tool that aids in confirming the diagnosis before surgery, especially in complicated pulmonary hydatidosis. Special stains for cytologic specimen should be used if the possibility of ruptured hydatid is thought to improve the diagnostic yield. The histopathology of the surgical specimen should be reviewed for associated secondary infection and fungal colonization.

Beta(2)-adrenergic receptor polymorphisms and response to salbutamol among Indian asthmatics*.

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.

Bronchoscopic closure of bronchopleural fistula using gelfoam.

Management of a persistent bronchopleural fistula (BPF) can be a therapeutic challenge. The etiological factors responsible for BPF include pulmonary tuberculosis, post-thoracic resection surgeries, trauma, malignancy, necrotising infections and rupture of lung abscess. The immediate management of BPF is drainage of the pleural cavity with insertion of an intercostal drainage tube. Patients with BPF may also require surgical intervention in the form of a wedge resection or lobectomy or muscle flap surgery. We report a case of a peripheral BPF secondary to a bacterial infection, which was successfully managed by the instillation of gelfoam via flexible bronchoscopy.