Acceptance and results of therapy with omalizumab in real world Kerala setting: reports from the ARTWORK study, Kerala, South India.

OBJECTIVE: Despite the availability of effective medications, only a minority of asthma patients achieve guideline defined asthma control. Treatment success depends on patient concurrence to the prescribed drug and adherence to treatment. It is therefore crucial to identify the patient preferences as well as attitudes towards asthma medications. Omalizumab is recommended as a preferred option in step 5 of asthma therapy. There have been few studies to address patient perspectives on omalizumab therapy in India. METHODS: This was a retrospective study. Patients with inadequate asthma control were considered for the study. Systematic evaluation was done to identify and correct modifiable factors that can worsen asthma control. Patients with persisting poor asthma control who were deemed suitable to receive this agent were evaluated with their attitudes toward acceptance or refusal and the reasons for opting out were noted. The patients who received omalizumab were followed up to determine the results of treatment and duration of adherence to therapy. RESULTS: Thirty-five patients out of 51 patients chose to avoid this drug. The reasons for opting out included erroneous perception of optimal asthma control, cost of therapy, and concern about adverse effects. Patients took omalizumab for a median duration of 6 months. Improved asthma control and decreased frequency of exacerbation was noted in all patients which persisted during the 6-month follow-up. CONCLUSIONS: The majority of patients needing step 5 therapy opt out of omalizumab. Cost of drug, duration of therapy and erroneous perception of good asthma control account for refusing treatment. Omalizumab affords excellent clinical benefits to patients who receive it, and the benefits extend beyond the duration of therapy.

Pneumothorax ex vacuo: Three cases of an uncommon entity.

Pneumothorax is a frequently encountered entity in pulmonary practice and can be primary or secondary. Traumatic and iatrogenic causes also account for a minority of cases presenting to the chest physician. The most common therapeutic intervention done is a tube thoracostomy in all but the mildest of cases. Pneumothorax ex vacuo is a distinctly uncommon entity that differs considerably from the rest of the pneumothorax cases in its pathogenesis, clinical manifestations, radiological findings, and management. Pneumothorax in this entity results from the sucking in of air into the pleural space caused by an exaggerated negative intrapleural pressure, which is most frequently secondary to acute lobar collapse. Symptoms attributable to pneumothorax per se are distinctly mild and the vital aspect of treatment is to relieve the bronchial obstruction. Tube thoracostomy fails to relieve the pneumothorax in such cases and should be avoided. We share three cases of pneumothorax ex vacuo encountered in our institution and alert clinicians of the presentation, radiology, and management of this uncommon condition.

Biological therapy for severe asthma - Indian perspectives and challenges.

Asthma is a complex and heterogeneous disease. Severe asthma makes up only a minority of asthma patients encountered in clinical settings but accounts for substantial healthcare utilisation in terms of manpower as well as economic allocation. The availability of monoclonal antibodies has a major impact on severe asthmatics and has provided excellent clinical results in properly selected patients. The discovery of new molecules might present uncertainties to clinicians as to the best agent to institute in an individual patient. The practice scenario in India is unique when it comes to the commercial availability of monoclonal antibodies, patient attitudes, and allocation of the healthcare budget. The present review dissects and summarises the available monoclonal antibodies for asthma treatment in India, the perspectives of Indian patients on biological therapy, and the challenges encountered by patients and physicians in this regard. We provide practical suggestions for utilising monoclonal antibodies and deciding on the optimal agent for a given patient.

Hospitalisation outcomes in pneumococcal-vaccinated versus -unvaccinated patients with exacerbation of COPD: results from the HOPE COPD Study.

Background: Infectious exacerbations are crucial events that dictate the natural course of COPD patients. Pneumococcal vaccination has been shown to decrease incidence of community-acquired pneumonia in COPD patients. There is a paucity of data on outcomes of hospitalisation in pneumococcal-vaccinated COPD patients in comparison with unvaccinated subjects. The objectives of the present study were to evaluate the difference in hospitalisation outcomes in pneumococcal-vaccinated versus -unvaccinated COPD subjects hospitalised with acute exacerbation. Methods: This was a prospective analytical study on 120 subjects hospitalised with acute COPD exacerbation. 60 patients with prior pneumococcal vaccination and 60 unvaccinated patients were recruited. Outcomes of hospitalisation such as mortality rate, need for assisted ventilation, length of hospital stay, need for intensive care unit (ICU) care and length of ICU stay were collected and compared between two groups with appropriate statistical tools. Results: 60% of unvaccinated patients (36 out of 60) required assisted ventilation, whereas only 43.3% of vaccinated subjects (26 out of 60) needed assisted ventilation (p-value of 0.04). Most of the secondary outcomes were better in the vaccinated group. The mean±SD length of ICU stay in the vaccinated group was 0.67±1.11 days compared to 1.77±1.89 days in the unvaccinated group. The mean±SD length of hospital stay was 4.50±1.64 days and 5.47±2.03 days in the vaccinated and unvaccinated group, respectively (p-value of 0.005). Conclusions: COPD patients who have received prior pneumococcal vaccination have better outcomes when they are hospitalised for an acute exacerbation. Pneumococcal vaccination may be recommended for all patients with COPD who are at risk of hospitalisation with acute exacerbation.

Inhaled corticosteroids and risk of tuberculosis-How bad is the risk?

Inhaled corticosteroids (ICS) have a central role in the management of obstructive airway diseases. Use of ICS in asthma and chronic obstructive pulmonary disease (COPD) is associated with a small but clear increase in incidence of pneumonia and tuberculosis. Since ICS use in obstructive airway diseases has beneficial effects with regard to symptoms, lung function, quality of life and exacerbations, denying the benefit of ICS solely based on this small elevated risk of pneumonias and tuberculosis is not justified. The present article attempts to elucidate mechanisms contributing to the increased risk, assesses the magnitude and risk factors of tuberculosis in patients using ICS and provides practical suggestions for practising clinicians.

Delayed lung function testing after COVID-19 to detect persistent lung function abnormalities - The DELTA - COVID-19 lung function study.

Background: Coronavirus disease 2019 (COVID-19) has made its presence felt as the worst pandemic witnessed till date in the 21st century. The mortality and morbidity associated with COVID-19 does not end with the acute pneumonia and respiratory failure and consequences extend well into the subsequent weeks to months in a minority. After recovery from severe disease, symptoms, lung function abnormalities and radiological changes are known to persist for varying length of time in a small proportion of patients. Various studies report different incidences of lung function abnormalities post-COVID-19. The present study describes the occurrence, severity, pattern and risk factors for persistent lung function abnormalities post-COVID-19 patients. Aim: The present study was aimed to find out the occurrence of persistent lung function abnormalities in patients hospitalised with COVID-19 at three months of discharge who had normal previous lung function prior to COVID-19. In those with persisting abnormal lung function, the severity, pattern and risk factors for persistent lung function abnormalities were also studied. Methods: The present study was a retrospective study in patients hospitalised with COVID-19 who had radiological evidence of pneumonia at admission. Patients with prior abnormal lung function were excluded from the study. Lung function was analysed with spirometry, 6-min walk test and diffusion capacity between day 85 and 95 of hospital discharge and the occurrence, severity and pattern of impairment was described. Lung function impairment was correlated with baseline characteristics and univariate regression analysis was done to identify risk factors for persisting functional impairment. Results: 39 patients were included in the study. Spirometry at follow up showed a restrictive ventilatory defect in 26 out of 39 patients (64%) and a normal study was noted in 12 patients. One patient had an obstructive ventilatory defect. Diffusion impairment was present in 27 patients and normal transfer factor was seen in 12 patients. The degree of diffusion impairment was mild in 16 patients and moderate in 11 patients. Univariate regression analysis revealed that age, history of systemic hypertension, severe hypoxia at presentation, and extent of lung involvement by CT chest were associated with lung function impairment. Conclusion: Almost two-thirds of patients hospitalised with COVID-19 pneumonia have persistent lung function abnormalities at three months post-discharge. Advanced age, severe disease and medical comorbidities increase the risk of persistent functional abnormalities.

COVID-19 presenting as acute transient flaccid limb paralysis.

Novel corona virus pandemic in 2020 has created havoc across the world. Since its entry into Indian subcontinent in February 2020, it has become the second most affected country in the world. In this context we wish to share the case of a young man who presented with periodic paralysis was eventually diagnosed to have COVID-19 infection. During this pandemic season, one has to be vigilant and think out of the box to identify COVID-19 infections even among the least suspicious cases.

Improving the yield of diagnostic medical thoracoscopy for undiagnosed exudative pleural effusions using a rigid diagnostic algorithm.

Background: Establishing the etiology of exudative pleural effusions in the setting of an unrewarding pleural fluid analysis often requires biopsies from the parietal pleura. However, it may be noted that diagnosis such as pulmonary embolism and connective tissue diseases can result in an exudative pleural effusion where a pleural biopsy can yield nonspecific results. Medical thoracoscopy (MT) is a minimally invasive procedure performed under local anesthesia or moderate sedation with excellent yield and favorable safety profile. We analyzed the diagnostic yield of MT for exudative pleural effusions after employing a rigid diagnostic algorithm. The study was undertaken to ascertain the yield of MT in establishing the diagnosis in diagnosis of exudative pleural effusions, to find out the relative contribution of pleural tuberculosis (TB) as a cause of undiagnosed exudative pleural effusion, to describe the etiology of undiagnosed exudative pleural effusion in patients undergoing MT and to determine the correlation between pleural fluid adenosine deaminase (ADA) levels and TB pleuritis in patients undergoing MT. Methods: This was a retrospective study. Patients with undiagnosed exudative pleural effusion were included in the study. MT was performed with semirigid thoracoscope (Olympus LTF 160) under local anesthesia and conscious sedation. Gross appearance and ADA level of pleural fluid were noted. Pleural biopsy material was subjected to histopathology examination and culture for mycobacteria along with cartridge-based nucleic acid amplification test for TB. The yield of MT for establishing the etiology of pleural effusion and the relative contribution of tuberculous pleuritis as a cause of undiagnosed pleural effusion was ascertained. Correlation of pleural fluid ADA levels was done with a final diagnosis of TB pleuritis in patients undergoing MT. Results: Twenty-five patients with undiagnosed exudative pleural effusion underwent thoracoscopy of which 16 were male and 9 were female. MT was able to establish the diagnosis in all cases, providing a diagnostic yield of 100%. Histopathological examination of biopsy specimens yielded a diagnosis of malignant involvement of pleura in 10 patients and granulomatous pleuritis consistent with TB in 14 patients. Pleural TB contributed to 60% of undiagnosed pleural effusions in the present study. The mean ADA value among those who turned positive was 56.338 and 35.300 among those who turned negative using genexpert, which was found to be statistically significant. A value of 31 IU/L showed a sensitivity of 93.3% and specificity of 99.8% and hence can be taken as a cut off value for the diagnosis of pleural TB based on receiver-operating characteristic analysis. Conclusion: TB contributed to 60% of undiagnosed exudative pleural effusions in the present study. MT had 100% yield in the diagnosis of undiagnosed exudative effusions. Pleural fluid ADA levels may help in differentiating TB versus malignant effusion.

Expecting the unexpected - Primary mediastinal large B cell lymphoma presenting as huge lung parenchymal mass.

The first possibility considered in the etiology of large lung masses is neoplastic lesions. The differential diagnoses of these masses include bronchogenic carcinoma, pulmonary sarcoma, primitive neuroectodermal tumor etc. Primary or secondary pulmonary parenchymal lymphomas presenting as large mass is distinctly rare. We share the case of a young lady who presented with a large left lung mass almost entirely replacing the left lung parenchyma, with associated intrathoracic lymphadenopathy. On evaluation she was proved to have primary mediastinal large B-cell lymphoma. Treatment with an aggressive chemotherapy regimen led to complete remission of the parenchymal and nodal disease. The uncommon radiological presentation and the excellent therapeutic response despite huge tumor load merit clinical attention.

Inhaled Formoterol-Fluticasone Single Inhaler Therapy in Asthma: Real-World Efficacy, Budget Impact, and Potential to Improve Adherence.

Asthma is the commonest chronic disease affecting airways in humans and has an increasing global disease burden. Inhaled corticosteroids (ICS) are the first-line therapeutic option for asthma, and addition of a long-acting beta 2-agonist (LABA) has been shown to improve asthma control. A combination of the two agents in a single inhaler is beneficial with regard to ease of administration and patient compliance. Various ICS-LABA formulations are available across various countries in the world, one among them being formoterol-fluticasone. Both formoterol and fluticasone have pharmacologic peculiarities which places the combination in a uniquely advantageous position when it comes to asthma therapy. The present review focuses on some of the, hitherto, less explored aspects of this combination inhaler such as real-world efficacy, impact on budget allocation, results of switch-over therapy, and potential to improve adherence to asthma treatment. It also provides practical recommendations on positioning it in real-world asthma management.

Efficacy of Omalizumab Therapy in an Asthmatic with Low IgE.

Asthma is one of the most common respiratory diseases encountered in clinical practice. Although the vast majority of asthmatics can be adequately controlled with inhaled steroids and other preventer medications, a small proportion remain uncontrolled. Anti-IgE treatment with omalizumab has been proposed in patients as a preferred approach in step 5 asthma therapy according to GINA guidelines. Although therapy with this molecule is approved for patients with atopic asthma and pretreatment serum IgE levels of 30-1500 only, there have been a few reports of its efficacy in subjects outside this reference IgE range. We report the case of a middle-aged lady with severe corticosteroid-dependent asthma and low serum IgE levels who was successfully treated with 9 months of omalizumab therapy. She gained good asthma control and was tapered off steroid use by the fifth month of therapy with omalizumab. The case report stresses the need for further investigation into expanding the spectrum of omalizumab usage in asthma beyond the current IgE suitability range.