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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., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2022 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Theophylline is a methylxanthine bronchodilator with a narrow therapeutic index and is prone to induce seizures, the mechanisms for which are not clearly defined. Free radicals have considerable neurotoxic potential and the present study evaluated the possible involvement of these bioactive moieties in aminophylline-induced seizures in mice. Aminophylline (50-250 mg/kg) induced convulsions and mortality in mice in a dose-dependent manner. The anti-oxidants, melatonin (25-100 mg/kg) and N-actylcysteine (100 and 200 mg/kg) attenuated aminophylline seizures and mortality. Similar antagonism of aminophylline seizures was also observed after pretreatments with nitric oxide (NO) synthase inhibitors, L-NAME (3 and 10 mg/kg) and 7-nitroindazole (10 and 30 mg/kg). Further, combined treatment with otherwise sub-effective doses of melatonin and L-NAME or 7-nitroindazole produced marked protective effects against these seizures. Aminophylline-induced seizures enhanced malondialdehyde (MDA) concentrations and NO metabolite (NOx) levels in the brain homogenates of mice, and these were attenuated by melatonin and L-NAME pretreatments. The results are suggestive of the possible involvement of free radicals (reactive oxygen and reactive nitrogen species) in the convulsiogenic effects of aminophylline.

Several indices have been suggested to express the bronchodilator response but there is no agreement on what is the ideal expression. The forced expiratory volume in I s (FEV1) was measured in 190 patients of bronchial asthma before and after inhalation of 200 micrograms salbutamol. Four different indices of bronchodilator response were calculated. The change in FEV1 was expressed as absolute value (delta FEV1), as a percentage of initial FEV1 (delta FEV1% initial), as a percentage of the predicted normal value (delta FEV1% predicted) and as a percentage of maximum achievable reversibility, i.e. the difference between predicted and initial values (delta FEV1% [predicted-initial]). A significant negative correlation was observed between delta FEV1 initial and initial FEV1% predicted (r = -0.33, P < 0.0001) but not delta FEV1 and initial FEV1% predicted, or between delta FEV1% predicted and initial FEV1% predicted. The values of delta FEV1% [predicted-initial] tended to reach towards infinity as the initial FEV1% predicted approached 100%. delta FEV1% predicted had similar sensitivity but greater specificity than delta FEV1% initial in detecting a true bronchodilator response. It was concluded that being dependent on the initial value, delta FEV1% initial was not an appropriate method to express the bronchodilator response. Although all other methods had limitations, delta FEV1 and delta FEV1% predicted appeared to be better indices.

The role of pre-operative short-term pulmonary rehabilitation in patients with chronic obstructive pulmonary disease who undergo coronary artery bypass graft surgery has been assessed for the first time prospectively. Forty-five patients posted for coronary artery bypass graft surgery were randomised to receive either short-term pulmonary rehabilitation (group I) or no such programme (group II). Patients of both the groups were evenly matched with respect to age, sex, body surface area, duration and severity of chronic obstructive pulmonary disease and coronary artery disease. Normal individuals who evenly matched with the study group were assessed for normal respiratory function parameters. Pre-operative and post-operative peak expiratory flow rate, inspiratory capacity, post-operative ventilation time, post-operative pulmonary complication and hospital stay were determined in both the groups. Peak expiratory flow rate (220.0 +/- 12.9 and 324.3 +/- 84.3 in group I, 218.0 +/- 16.4 and 260.5 +/- 35.2 in group II) and inspiratory capacity (844.0 +/- 147.4 and 1100.0 +/- 158.1 in group I, 830.0 +/- 117.4 and 1090 +/- 137 in group II) were significantly lower before and after surgery respectively in both groups compared to normal values. Even though both groups showed a significant rise in post-operative peak expiratory flow rate and inspiratory capacity after surgery, the post-operative peak expiratory flow rate and inspiratory capacity in group I was significantly higher than in group II. In group I, the post-operative ventilation time (24.5 +/- 6.00 hours), post-operative complications (n = 4) and hospital stay (12.4 +/- 3.6 days) were significantly lower than in group II (35.2 +/- 22.3 hours, n = 11, 18.8 +/- 6.6 days respectively). These data suggest that short-term pulmonary rehabilitation is feasible and effective in improving pulmonary functions before and after surgery and in reducing surgical morbidity and cost of medical care significantly.

Bronchoalveolar lavage (BAL) studies in 20 patients at Bhopal, 1.3 +/- 0.4 yr and 2.7 +/- 0.6 yr after toxic gas exposure had revealed that the lower respiratory tract inflammation had progressed from initial macrophage alveolitis to macrophage-neutrophilic alveolitis. The interval between the two lavages was 1.4 +/- 0.6 yr. BAL studies in a new group of 24 patients 5.1 +/- 1.0 yr after exposure had confirmed chronic inflammation of the lower respiratory tract as evidenced by macrophage-neutrophilic alveolitis in these subjects as well. Clinical, radiographic and pulmonary function abnormalities were persistent in a proportion of subjects in both groups. Fibronectin (FN) levels were estimated in BAL fluid in 41 patients. Elevated FN levels were seen in 12 (29.3%) subjects and nine of these 12 had radiographic abnormalities. Severely exposed subjects (n = 30) had significantly higher BAL fibronectin levels compared to normal subjects and mild/moderately exposed subjects. Repeat FN estimations in BAL samples from 10 patients had revealed that five had abnormally high FN including three who had high FN on both occasions. The number of patients showing abnormal decline in pulmonary function was higher in patients with elevated FN than in patients with normal FN. Thus, persisting clinical, roentgenographic and ventilatory abnormalities, as well as macrophage-neutrophilic alveolitis along with abnormally elevated FN levels in a proportion of subjects, suggest the possibility that lung fibrosis can occur in subjects exposed to toxic gas at Bhopal.

Three radiologically and bacteriologically confirmed pulmonary tuberculosis patients had eosinophilic pneumonia, as demonstrated by BAL. In two patients, pulmonary eosinophilia was present only at the site of the lesion and the third had eosinophilia in both peripheral blood and lung. There was complete elimination of the eosinophilic inflammatory process in two patients who had successfully completed antituberculosis treatment.

Fifty patients with tropical eosinophilia were studied clinically and physiologically, before and after a standard 3-week course of diethylcarbamazine. Before treatment the main physiological abnormality was a reduction in the carbon monoxide transfer factor. One month after the start of treatment most patients had shown a marked symptomatic improvement, but peripheral blood eosinophilia persisted in 52%, radiographic abnormalities in 44%, cough in 22% and chest signs in 8%. Significant improvement was noted in almost all aspects of lung function including blood gases, but the mean values for forced expiratory volume in one second, forced vital capacity, transfer factor and transfer coefficient continued to be significantly lower than predicted values. This study demonstrates the incomplete reversal of clinical, haematological, radiological and physiological changes in tropical eosinophilia one month after starting a 3-week course of diethylcarbamazine.

Our previous morphologic studies in the rat demonstrated that exposure to lead during the preweaning period induced delays in the maturation of late-developing regions of the hippocampal formation at 15 days of age, followed by normal development or hypertrophy of the same areas in young adulthood. The present study was carried out to determine whether or not subtle or latent effects of such exposure to lead may be unmasked with the additional challenge of aging. To do this, mid-dorsal sections of the hippocampal formation from middle-aged (578-631 days old) Long-Evans control rats and from rats exposed to lead from birth until weaning via dams drinking 0.2% lead acetate were analyzed by light and electron microscopy. Exposure to lead did not alter areas of either neuropil or neuronal layers of the hippocampus or the dentate gyrus or the numbers per section or numerical densities (numbers per unit area) of neurons in hippocampal CA3 stratum pyramidale or dentate stratum granulosum. It did reduce mean size of complex invaginated mossy fiber synapses without altering their numbers in the proximal (close to dentate gyrus) mossy fiber zone, which was the zone also affected at 15 and 90 days of age in our previous studies.

In the hippocampus of young and aged rats, lysosomal acid phosphatase and beta-glucuronidase were localized by enzyme histochemistry to the pyramidal and granule cells and to the mossy fiber zone (acid phosphatase only). Following a unilateral entorhinal lesion, enhancement in enzyme staining was observed within GFA (glial fibrillary acidic) protein-positive astrocytes and in cells resembling microglia and oligodendroglia in the ipsilateral dentate outer molecular layer and the hippocampal stratum lacunosum-moleculare. In young animals, these changes, first detected on day 2 post-lesion, were maximum on days 4 and 10 post-lesion and declined subsequently. The aged animals exhibited a delayed time-course of enzyme changes with minimal increases on days 2 and 4 post-lesion and greater increases on days 10 and 30 and gradual diminution thereafter. The delayed lysosomal response in the aged animal paralleled a reduction in the induction of glial cells following the lesion. Our findings suggest that the previously reported impairment in the clearing of degeneration debris in the aged animal is mediated by reduced glial induction and delayed glial lysosomal activation.