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Allergic bronchopulmonary aspergillosis (ABPA) is an inflammatory disease caused by immunologic reactions initiated against Aspergillus fumigatus colonizing the airways of patients with asthma and cystic fibrosis. The common manifestations include treatment-resistant asthma, transient and fleeting pulmonary opacities and bronchiectasis. It is believed that globally there are about five million cases of ABPA, with India alone accounting for about 1.4 million cases. The occurrence of ABPA among asthmatic patients in special clinics may be as high as 13 per cent. Thus, a high degree of suspicion for ABPA should be entertained while treating a patient with bronchial asthma, particularly in specialized clinics. Early diagnosis and appropriate treatment can delay (or even prevent) the onset of bronchiectasis, which suggests that all patients of bronchial asthma should be screened for ABPA, especially in chest clinics. The current review summarizes the recent advances in the pathogenesis, diagnosis and management of ABPA.

Severe coronavirus disease (COVID-19) is currently managed with systemic glucocorticoids. Opportunistic fungal infections are of concern in such patients. While COVID-19 associated pulmonary aspergillosis is increasingly recognized, mucormycosis is rare. We describe a case of probable pulmonary mucormycosis in a 55-year-old man with diabetes, end-stage kidney disease, and COVID-19. The index case was diagnosed with pulmonary mucormycosis 21 days following admission for severe COVID-19. He received 5 g of liposomal amphotericin B and was discharged after 54 days from the hospital. We also performed a systematic review of the literature and identified seven additional cases of COVID-19 associated mucormycosis (CAM). Of the eight cases included in our review, diabetes mellitus was the most common risk factor. Three subjects had no risk factor other than glucocorticoids for COVID-19. Mucormycosis usually developed 10–14 days after hospitalization. All except the index case died. In two subjects, CAM was diagnosed postmortem. Mucormycosis is an uncommon but serious infection that complicates the course of severe COVID-19. Subjects with diabetes mellitus and multiple risk factors may be at a higher risk for developing mucormycosis. Concurrent glucocorticoid therapy probably heightens the risk of mucormycosis. A high index of suspicion and aggressive management is required to improve outcomes.

Allergic bronchopulmonary aspergillosis (ABPA) is a severe asthma endotype arising from dysregulated immune responses to in susceptible individuals. ABPA is characterized by exaggerated type 2 immune responses, markedly elevated serum total IgE and -specific IgE and IgG levels, peripheral blood eosinophilia, and imaging abnormalities, including bronchiectasis and mucus impaction. Genetic predisposition involving HLA genotypes and immune-related polymorphisms contributes to disease susceptibility. The 2024 International Society of Human and Animal Mycology guidelines provide standardized criteria that integrate clinical, immunological, and radiological parameters to identify ABPA and distinguish it from overlapping diagnoses. Management employs a dual approach: anti-inflammatory therapy with systemic corticosteroids targets dysregulated immunity, while antifungal therapy with triazoles reduces airway fungal burden. The relapsing-remitting disease course necessitates systematic monitoring using clinical assessment, total IgE levels, and serial imaging to detect relapses, distinguish them from asthma exacerbations or infections, and optimize treatment intensity. Despite substantial progress in understanding the pathobiology of ABPA, high-quality evidence for optimal management strategies remains limited. Future research should focus on precision medicine approaches, novel biomarkers, and inhaled antifungal therapies to improve outcomes in this severe asthma phenotype. This review provides clinicians with comprehensive information on the pathobiology, diagnosis, classification, and evidence-based management strategies for ABPA, aiming to improve outcomes for patients with this severe asthma endotype.

Chronic pulmonary aspergillosis has a 5-year mortality of 50–80% globally, and the optimal duration of treatment for chronic pulmonary aspergillosis remains unclear. We aimed to compare the effect of 6-months of oral itraconazole with 12-months of oral itraconazole on chronic pulmonary aspergillosis clinical outcomes. In this single-centre, open-label, randomised controlled trial conducted in one chest clinic in Chandigarh, India, we screened consecutive patients with chronic pulmonary aspergillosis who were naive to antifungal treatment and randomised eligible patients, using block randomisation, to receive a starting dose of 400 mg/day of oral itraconazole for either 6 months or 12 months. There was no masking of participants or investigators. We excluded patients who were unable to provide informed consent; had an intake of any antifungal drugs for more than 3 weeks in the preceding 6 months; had active Mycobacterium tuberculosis or non-tuberculous mycobacterial pulmonary disease; and had allergic, subacute, or invasive forms of aspergillosis. The primary outcome was the proportion of patients having relapse 2 years after treatment initiation. We performed an intention-to-treat analysis for all outcomes. The study is registered with ClinicalTrials.gov, NCT03920527. We recruited participants between Feb 14, 2019, and Aug 30, 2019, and the last follow-up was completed on Aug 31, 2021. We screened 250 patients, of which 164 were included in the trial. 81 patients were randomised to the 6-month group and 83 patients were randomised to the 12-month group. The study population was 78 (48%) women and 86 (52%) men, and the mean age of participants was 44·3 (SD 13·3) years. The proportion of patients experiencing relapse was significantly lower in the 12-month group, 31 (38%) had a relapse in the 6-month group compared with 8 (10%) in the 12-month group, with an absolute risk reduction of 0.29 [95% CI 0·16–0·40]. The mean time to first relapse was 23 months in the 12-month group, which is significantly longer than the mean of 18 months in the 6-month group (p<0.0001). There were 16 deaths in total, eight in each group. Ten (12%) of 81 patients in the 6-months group and 18 (22%) of 83 patients in the 12-months group had adverse effects, with none requiring treatment modification. Nausea and anorexia were the most common adverse events in both groups. Treatment of chronic pulmonary aspergillosis with 12 months of oral itraconazole was superior to 6 months of oral itraconazole in reducing relapses at 2 years. Itraconazole should be given for at least 12 months for treating chronic pulmonary aspergillosis. None. For the Hindi translation of the abstract see Supplementary Materials section.

Pleural fluid adenosine deaminase (ADA) is a useful diagnostic test for tuberculous pleural effusion (TPE), but its exact threshold and accuracy in clinical decision-making is unclear. We aimed to assess diagnostic performance of ADA in TPE and to clarify its optimal diagnostic threshold. We searched PubMed, Embase, and Cochrane Library databases for articles indexed up to October 2018. We included English language studies that provided both sensitivity and specificity of ADA in TPE diagnosis. Summary estimates for sensitivity and specificity were obtained through bivariate random effects model, both overall and at prespecified threshold ranges of <36, 40±4, 45-65 and >65 IU/L. We retrieved 2162 citations, and included 174 publications with 27009 patients. All studies showed high risk of bias. Summary sensitivity, specificity and diagnostic odds ratio estimates were 0.92 (95% CI 0.90-0.93), 0.90 (95% CI 0.88-0.91) and 97.42 (95% CI 74.90-126.72) respectively. 65 studies with ADA threshold of 40±4 IU/L showed summary sensitivity and specificity of 0.93 (95% CI 0.90-0.95) and 0.90 (95% CI 0.87-0.91) respectively. Four studies with ADA threshold >65 IU/L showed summary sensitivity and specificity of 0.86 (95% CI 0.61-0.96) and 0.94 (95% CI 0.80-0.99) respectively. ADA levels in pleural fluid show good diagnostic accuracy in diagnosis of TPE; however, all included studies showed high risk of bias. It was not possible to derive any firm inference on relative clinical utility of different diagnostic thresholds.

COVID-19 is an ongoing pandemic with many challenges that are now extending to its intriguing long-term sequel. 'Long-COVID-19' is a term given to the lingering or protracted illness that patients of COVID-19 continue to experience even in their post-recovery phase. It is also being called 'post-acute COVID-19', 'ongoing symptomatic COVID-19', 'chronic COVID-19', 'post COVID-19 syndrome', and 'long-haul COVID-19'. Fatigue, dyspnea, cough, headache, brain fog, anosmia, and dysgeusia are common symptoms seen in Long-COVID-19, but more varied and debilitating injuries involving pulmonary, cardiovascular, cutaneous, musculoskeletal and neuropsychiatric systems are also being reported. With the data on Long-COVID-19 still emerging, the present review aims to highlight its epidemiology, protean clinical manifestations, risk predictors, and management strategies. With the re-emergence of new waves of SARS-CoV-2 infection, Long-COVID-19 is expected to produce another public health crisis on the heels of current pandemic. Thus, it becomes imperative to emphasize this condition and disseminate its awareness to medical professionals, patients, the public, and policymakers alike to prepare and augment health care facilities for continued surveillance of these patients. Further research comprising cataloging of symptoms, longer-ranging observational studies, and clinical trials are necessary to evaluate longterm consequences of COVID-19, and it warrants setting-up of dedicated, post-COVID care, multidisciplinary clinics, and rehabilitation centers. Keywords: ongoing symptomatic COVID-19, post-COVID-19 syndrome, chronic COVID, Long-COVID-19, post-COVID, Long-COVID

Both itraconazole and voriconazole are used to treat chronic pulmonary aspergillosis. However, treatment success with itraconazole is only around 65–70%. Voriconazole, with its lower minimum inhibitory concentrations and better oral bioavailability, might offer improved outcomes, but no head-to-head comparison has been conducted to date. We aimed to evaluate whether oral voriconazole is superior to itraconazole in treating chronic pulmonary aspergillosis. This single-centre, prospective, open-label, superiority trial was conducted at the chest clinic of a tertiary care hospital in Chandigarh, India. We enrolled treatment-naive adults aged 18 years or older with chronic cavitary pulmonary aspergillosis or chronic fibrosing pulmonary aspergillosis. We excluded those who denied consent, received any antifungal azoles for more than 3 weeks in the previous 6 months, or had other forms of aspergillosis. Participants were randomly assigned 1:1 to receive 200 mg twice daily of oral itraconazole or oral voriconazole for 6 months, using a computer-generated randomisation sequence with variable block sizes (4–8). Participants, staff administering the interventions, clinical outcome assessors, and data analysts were not masked to treatment assignment; a radiologist masked to clinical details and treatment allocation evaluated chest images. The primary outcome was the proportion of participants achieving a favourable response (clinical and radiological stability or improvement) at 6 months in the modified intention-to-treat population, which included all participants who received at least one dose of the allocated treatment. The safety analyses (a secondary outcome) were also performed in the modified intention-to-treat population. This trial is registered at ClinicalTrials.gov (NCT04824417) and is complete. Between April 15, 2021, and May 31, 2024, 150 individuals were screened, and 116 were randomly assigned to receive itraconazole (n=58) or voriconazole (n=58). Of the 116 participants, 74 (64%) were men, 42 (36%) were women, and the mean age was 45·9 years (SD 14·4). All participants received at least one dose of the study drug and were included in the primary analysis. The proportion of participants achieving a favourable response at 6 months was similar in both groups (69% [40 of 58] receiving voriconazole vs 67% [39 of 58] receiving itraconazole; absolute risk reduction –0·02 [95% CI –0·2 to 0·15], p=0·84). Voriconazole was associated with significantly more treatment-related adverse events than itraconazole (55% [32 of 58] of participants receiving voriconazole vs 34% [20 of 58] receiving itraconazole, p=0·025). There were four deaths, all in the voriconazole group; none were directly attributable to the treatment. Voriconazole was not superior to itraconazole for treating chronic pulmonary aspergillosis and was associated with a significantly higher incidence of adverse events. Our findings support the continued use of itraconazole as the preferred therapy for chronic pulmonary aspergillosis, although voriconazole remains a reasonable alternative. The choice between the two agents should be guided by factors such as patient tolerance, drug availability, and cost considerations. Cipla Pharmaceuticals, India.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex pulmonary disorder caused by dysregulated immune responses against . The disorder usually complicates the course of patients with asthma and cystic fibrosis. Patients with ABPA most often present with asthma that is poorly controlled despite inhaled corticosteroids and long-acting β2 agonists. The treatment of ABPA is complicated due to the occurrence of recurrent exacerbations and spontaneous remissions. The drugs used for treating ABPA include systemic glucocorticoids, antifungal agents and biologics, each with its own benefits and drawbacks. In this review, we illustrate the treatment pathway for ABPA in different situations, using a case-based approach. In each case, we present the options for treatment based on the available evidence from recent clinical trials.