Expert Opinion on Usage of Pidotimod in Adult Patients with Chronic Obstructive Pulmonary Disease: An Indian Perspective.

India has a disproportionately high burden of acute and chronic pulmonary diseases. In India, 65 million suffer from non-communicable respiratory diseases. The outbreak of the novel coronavirus disease 2019 (COVID-19) had worsened the situation. Patients affected with COVID-19 with a previous history of comorbidities, such as COPD and chronic lung diseases, had the worst prognosis, resulting in adverse outcomes, such as acute respiratory distress syndrome (ARDS) and pneumonia. Immune modulation strategies have since gained a lot of traction amongst practitioners. Modulation of the immune system with Pidotimod along with standard-of-care (SOC) treatment has proven efficacious in the past two decades in patients with recurrent respiratory tract infections (RRTIs), bronchitis, COPD, and pneumonia. In this article, we have reviewed the current unmet needs in the management of COPD in India and evaluated the usage of Pidotimod in adult COPD patients based on expert panel discussion.

Consensus Document on Home Nebulization for Maintenance Treatment of Obstructive Airway Diseases: A Joint Initiative by the National Allergy Asthma Bronchitis Institute (NAABI) and Chest Research Foundation (CRF).

Recent years have seen an increase in the use of nebulizers for delivering maintenance therapy in obstructive airway diseases (OADs) such as asthma and chronic obstructive pulmonary disease (COPD). The probable factors associated with this increase at home are: convenience of drug delivery, technological advances making the nebulizer equipment more efficient and portable, increase in the prevalence of OADs and the ageing population which may impact the optimal use of handheld inhalers such as pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs). Although there is increase in the use of maintenance therapy with nebulization, there has been no such increase in the evidence base available for the appropriate use of nebulizers. The last international guidelines were published in 2001. Hence there is a need to address this knowledge gap especially with the widespread use of home nebulization in India. With this objective, we organized a consensus meeting to address certain critical questions pertaining to the use of nebulizers for maintenance treatment in OADs. This article presents the findings of the consensus panel on the use of maintenance treatment of OADs with nebulization at home.

Importance of Therapeutic Drug Monitoring of Rifampicin.

Therapeutic Drug Monitoring (TDM) is a routinely practised clinical laboratory technique which aids the clinicians with a clear clinical judgement of the drug therapy and optimize the doses if necessary. Rifampicin is the most important and potent component of first line therapy of tuberculosis (TB). Several factors like age, weight, gender, doses and formulations, gastro-intestinal disorders, ethnicity etc alter the absorption and bioavailability of rifampicin thus altering the drug levels. Low plasma levels of rifampicin may play a plausible role in slow response to therapy, treatment failure or relapse or acquired drug resistance. TB Patients with further complicated conditions like diabetes or HIV are at an increased risk for poor drug absorption and drug-drug interactions. A standard treatment regimen may be inadequate for some cases as the clinical status of patients vary from case to case. TDM can be used as a clinical tool for identifying patients at high risk of treatment failure, delayed response, drug-drug interactions and help optimization of therapy. In the past two decades numerous reports of TDM of anti-tuberculosis drugs have been reported wherein low rifampicin levels have been a major concern. Rifampicin exhibit concentration dependent killing of mycobacteria. A 2 hour post-dose sample approximates the peak plasma rifampicin concentration (Cmax) and is recommended for TDM of rifampicin. An additional 6 hour sample may be collected to distinguish between delayed absorption and malabsorption. Combined with clinical and bacteriological data, TDM can help clinicians treat slow response / complicated TB 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.

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.

Central retinal vein occlusion in a patient after being commenced on sildenafil citrate for pulmonary arterial hypertension.

A 75-year-old female was commenced on sildenafil for the treatment of pulmonary arterial hypertension (PAH) secondary to chronic obstructive pulmonary disease (COPD). She reported blurring of vision within 72 hours after starting treatment and was found to have a central retinal vein occlusion (CRVO). Such an occurrence is the second case reported to date, and we review the possible mechanisms and literature on the subject.

A patient with hypercoagulable state due to tuberculosis.

A 55-year-old male patient presented with status epilepticus following prolonged fever. Investigations revealed miliary opacities in lungs that were diagnosed as tubercular after thoracoscopic lung biopsy. Wide derangement of coagulation parameters was found, indicating a pro-coagulent state. There was evidence of widespread thrombosis.

Hermansky-Pudlak syndrome.

We present a rare disease condition Hermansky-Pudlak syndrome in a 33-year-old male. He was born of a consanguineous marriage, had occulo-cutaneous albinism, nystagmus, decreased visual acuity, refractory errors, pulmonary fibrosis and granulomatous inflammation of the colon. In spite of all the classical features of this genetic disorder he was labeled to have disseminated tuberculous infection with a drug resistant strain for many years till the actual diagnosis was made on the basis of a strong clinical suspicion. We report this rare condition which might be misdiagnosed as tuberculosis.

Pidotimod: In-depth review of current evidence.

Pidotimod, an immunostimulant, is researched for over two decades. Current evidence indicates its utility in a variety of indications in children as well as in adults. Its immunostimulant activity has been firmly established in the management of recurrent respiratory infections in children with or without asthma. Compared to standard of care alone, addition of pidotimod to standard of care significantly prevents the recurrences and reduces the severity and duration of acute episodes, ultimately resulting in reduced visits to pediatric clinics and lower absenteeism at school. In adults, pidotimod is effective in the prevention and treatment of acute infectious exacerbations of chronic bronchitis and chronic obstructive pulmonary disease (COPD). Further, it has been evaluated in indications such as pneumonia, hand-food-mouth disease, bronchiectasis, and chronic idiopathic urticaria. From a total of 32 studies conducted in child (24 studies) and adult (8 studies) population, this in-depth review discusses the current evidence of pidotimod. With further exploration, the immunostimulant activity of pidotimod might be extended to different immunological disorders.

Pneumococcal disease burden from an Indian perspective: Need for its prevention in pulmonology practice.

Globally, pneumococcal diseases are a significant public health concern. They are preventable and frequently occur among older adults. Major risk factors for the disease are extremes of age, alcohol intake, smoking, air pollution, and comorbid conditions (diabetes, chronic obstructive pulmonary disease, chronic kidney disease, liver disease, and heart disease). Risk factors, coupled with limited disease-burden data and the emergence of antibiotics resistance, are hindering the effective management of the disease in older adults. Various global guidelines recommend pneumococcal vaccines for the prevention of pneumococcal diseases, as they reduce disease burden, hospitalization, and mortality rates among patients with comorbid conditions. Besides being an integral part of childhood immunization, these vaccines are advocated by various Indian healthcare bodies/groups for older and younger adults with certain medical conditions. The article presents an overview of the closed-door discussion by the Indian pulmonary experts on the scientific evidence and clinical practice followed for the prevention of pneumococcal disease in India.

Management of lower respiratory tract infection in outpatient settings: Focus on clarithromycin.

Lower respiratory tract infection (LRTI) is a broad terminology which includes acute bronchitis, pneumonia, acute exacerbations of chronic obstructive pulmonary disease/chronic bronchitis (AECB), and acute exacerbation of bronchiectasis. Acute LRTIs (ALRTIs) are one of the common clinical problems in community and hospital settings. Management of community-acquired pneumonia (CAP) and AECB may pose challenges because of diagnostic difficulty in differentiating infections caused by typical and atypical microorganisms and rising rates of antimicrobial resistance. Beta-lactam antibiotics, macrolides, and fluoroquinolones are routinely prescribed medicines for the management of ALRTIs. Macrolides are time-tested and effective agents for the treatment of LRTIs. Clarithromycin, a macrolide, offers several benefits in the management of ALRTIs. In this article, we discuss the management approach of LRTIs with focus on clarithromycin in the management of mild-to-moderate LRTIs (CAP and AECB), i.e., in outpatient settings.

Challenges in diagnosing Sarcoidosis in tuberculosis endemic regions: Clinical scenario in India.

 Sarcoidosis is a chronic, systemic disease of unknown etiology that affects multiple organs. The disease was considered rare in developing countries like India. More recently sarcoidosis is being increasingly diagnosed in countries where tuberculosis continues to be endemic. There is a general perception among physicians that the prevalence of sarcoidosis has increased over the last two decades in countries like India. This may be true but could also be related to better awareness of the condition, availability of improved diagnostic facilities and the increased ability of physicians to differentiate it from tuberculosis. In India, diagnosis of tuberculosis is entertained first in patients who may have sarcoidosis and thus, it is very likely for sarcoidosis to be misdiagnosed as tuberculosis, owing to the high prevalence of tuberculosis and clinicoradiological resemblance to the disease. This editorial highlights the challenges in diagnosing tuberculosis in countries where tuberculosis still continues to be endemic.

Chronic dry cough: Diagnostic and management approaches.

Cough is the most common symptom for which medical treatment is sought in the outpatient setting. Chronic dry cough poses a great diagnostic and management challenge due to myriad etiologies. Chronic cough has been commonly considered to be caused by gastroesophageal reflux, post-nasal drip or asthma. However, recent evidences suggest that many patients with these conditions do not have cough, and in those with cough, the response to specific treatments is unpredictable at best. This raises questions about the concept of a triad of treatable causes for chronic cough. This article discusses the mechanism and etiology of cough, along with recent advances in the field of cough, highlighting some of the diagnostic and management challenges.