Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.

Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

Acute Invasive Pulmonary Aspergillosis Complicating Allergic Bronchopulmonary Aspergillosis: Case Report and Systematic Review.

Aspergillus fumigatus can cause a variety of pulmonary syndromes including allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis and invasive pulmonary aspergillosis (IPA). Occurrence of IPA and ABPA in the same patient is rare as the risk factors for ABPA and IPA are different. We describe a 45-year-old male with ABPA treated with oral methylprednisolone and itraconazole, who developed acute respiratory failure secondary to IPA, a month later. The patient subsequently improved after systemic antifungal therapy. Presumably, itraconazole by inhibiting CYP3A4 enzyme caused an increase in plasma methylprednisolone levels. This probably led to a profound immunosuppressed state, which predisposed to the development of IPA. We performed a systematic review and identified nine cases of IPA following ABPA. The disease course is fulminant, and only three of the nine patients survived. Physicians treating ABPA patients should be aware of this potentially fatal overlap. Clinical suspicion and early diagnosis are crucial to improve the patient outcomes.

Clofazimine pulmonary crystal deposition syndrome: a case of pseudo haemoptysis.

Clofazimine is an antimycobacterial, anti-inflammatory agent used in the management of leprosy and multidrug-resistant (MDR) tuberculosis. It has high oral bioavailability and poor solubility because of which prolonged administration of the drug results in its accumulation as intracellular biocrystals in tissue macrophages. We describe the case of a female patient in her early 30s who was on therapy for MDR tuberculosis. She presented with streaky haemoptysis of 6 months. Radiographic examination showed no abnormality in pulmonary vasculature and parenchyma. Bronchoscopy showed diffuse red-coloured flecks in tracheal and bronchial mucosa. The retrieved bronchoalveolar lavage (BAL) fluid was reddish-purple in colour. Microscopic examination of BAL fluid showed reddish clofazimine crystal deposition in alveolar macrophages. Serum and BAL clofazimine levels were performed using high performance liquid chromatography which confirmed high drug levels. She developed reddish discolouration of the skin during therapy due to clofazimine deposition. A diagnosis of pulmonary clofazimine crystal deposition syndrome causing pseudohaemoptysis was established.

Non-resolving pneumonia: primary pulmonary MALT lymphoma.

Mucosa-associated lymphoid tissue (MALT) lymphoma is an uncommon extranodal low-grade B-cell lymphoma. Pulmonary MALT lymphomas originate from bronchial MALT and are also referred to as bronchial-associated lymphoid tissue lymphomas. MALT lymphomas of the lung are slow-growing tumours and usually present as asymptomatic chronic alveolar opacities visible on chest radiographs or with non-specific pulmonary symptoms. Here we described a case of a male patient in his early 50s with cough and chest pain for 4 years. His CT chest scan showed consolidation in the lingula and left lower lobe. Histopathology of the specimen obtained from cryobiopsy of the lung lesion showed a dense monomorphic lymphoid infiltrate, and immunohistochemistry confirmed the diagnosis of MALT lymphoma. The prognosis of pulmonary MALT lymphomas is good with >80% 5-year survival rates. This case highlights that MALT lymphoma should be considered as a differential diagnosis while evaluating cases with non-resolving consolidation.

Risk factors, mortality, and predictors of survival in COVID-19-associated pulmonary mucormycosis: a multicentre retrospective study from India.

OBJECTIVES: To compare COVID-19-associated pulmonary mucormycosis (CAPM) with COVID-19-associated rhino-orbital mucormycosis (CAROM), ascertain factors associated with CAPM among patients with COVID-19, and identify factors associated with 12-week mortality in CAPM. METHODS: We performed a retrospective multicentre cohort study. All study participants had COVID-19. We enrolled CAPM, CAROM, and COVID-19 subjects without mucormycosis (controls; age-matched). We collected information on demography, predisposing factors, and details of COVID-19 illness. Univariable analysis was used to compare CAPM and CAROM. We used multivariable logistic regression to evaluate factors associated with CAPM (with hypoxemia during COVID-19 as the primary exposure) and at 12-week mortality. RESULTS: We included 1724 cases (CAPM [n = 122], CAROM [n = 1602]) and 3911 controls. Male sex, renal transplantation, multimorbidity, neutrophil-lymphocyte ratio, intensive care admission, and cumulative glucocorticoid dose for COVID-19 were significantly higher in CAPM than in CAROM. On multivariable analysis, COVID-19-related hypoxemia (aOR, 2.384; 95% CI, 1.209-4.700), male sex, rural residence, diabetes mellitus, serum C-reactive protein, glucocorticoid, and zinc use during COVID-19 were independently associated with CAPM. CAPM reported a higher 12-week mortality than CAROM (56 of the 107 [52.3%] vs. 413 of the 1356 [30.5%]; p = 0.0001). Hypoxemia during COVID-19 (aOR [95% CI], 3.70 [1.34-10.25]) and Aspergillus co-infection (aOR [95% CI], 5.40 [1.23-23.64]) were independently associated with mortality in CAPM, whereas surgery was associated with better survival. DISCUSSION: CAPM is a distinct entity with a higher mortality than CAROM. Hypoxemia during COVID-19 illness is associated with CAPM. COVID-19 hypoxemia and Aspergillus co-infection were associated with higher mortality in CAPM.

Pleural Pustule-a Novel Thoracoscopic Appearance of Pleural Tuberculosis.

BACKGROUND: Thoracoscopic pleural biopsy is the gold standard for diagnosing tubercular pleural effusion (TPE). Various thoracoscopic appearances like sago grain nodules, caseous necrosis, and adhesions have been described in TPE. However, none of these have high specificity for diagnosing TPE. In this study we evaluate a novel finding on thoracoscopy, the " Pleural Pustule." METHODS: This is a retrospective analysis of patients who underwent thoracoscopy for undiagnosed pleural effusion. Visual inspection of the pleura was performed to identify abnormalities. Biopsies were obtained from those areas and sent for histopathology, acid fast bacillus (AFB) smear, culture, and Xpert MTB/Rif assay. Pleural pustule was defined as a pus filled nodule on the pleural surface. RESULTS: Of the 259 patients included, 92 were diagnosed with TPE. Pleural pustule(s) were identified in 16 patients with TPE. Presence of pleural pustule had a sensitivity, specificity, positive predictive value, and negative predictive value of 17.4%, 100%, 100% and 68.7%, respectively, for diagnosing TPE. Histopathology of pleural pustule demonstrated necrotizing granulomas in all. In patients with pleural pustule, a microbiological diagnosis of tuberculosis was achieved in 93.7% patients (AFB smear, Xpert MTB/Rif assay, and MTB culture positive in 31.3%, 93.7%, and 43.7% cases, respectively). There is a strong association between pleural pustule and positive Xpert MTB/Rif assay ( P =0.002) and microbiologic confirmation of diagnosis ( P =0.017). CONCLUSION: The presence of pleural pustule on thoracoscopy has a high positive predictive value for TPE. In tuberculosis-endemic countries, this can be considered suggestive for TPE. When identified, a biopsy from the pleural pustule should be performed as it will likely yield a positive microbiologic diagnosis.

Atypical mycobacterial infection masquerading as an endobronchial growth in an immunocompromised host.

Non-tuberculous mycobacteria (NTM) are ubiquitous organisms. Endobronchial growth as a presenting feature of NTM disease is uncommon. Here we present a case of a patient with retroviral disease on antiretroviral therapy, presenting with cough, wheezing and exertional dyspnoea. High-resolution CT showed a partial obstruction of the left main bronchus (LMB). Bronchoscopy showed an endobronchial growth in the distal LMB. An endobronchial biopsy showed non-necrotising granulomas; bronchial wash for acid-fast bacilli was positive and culture grew Mycobacterium avium complex. He was treated with a combination therapy of clarithromycin, rifampicin and ethambutol. Repeat bronchoscopy after 6 weeks of therapy showed complete resolution of the endobronchial growth.

Iatrogenic Cushing's syndrome in a case of allergic bronchopulmonary aspergillosis treated with oral itraconazole and inhaled budesonide.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus that occurs in patients with asthma or cystic fibrosis. Here, we report a case of a young female with bronchial asthma who presented to our hospital with worsening breathlessness on exertion. She was diagnosed to have ABPA and was initiated on oral itraconazole while continuing inhaled long acting beta-2 adrenergic agonist and medium dose inhaled corticosteroid (ICS) for her asthma. Three months after initiation of therapy, the patient had significant improvement in breathlessness. However, she had weight gain, facial puffiness, increased facial hair and development of striae on her inner thighs, calf and lower abdomen. Her serum cortisol levels were found to be suppressed and hence a diagnosis of iatrogenic Cushing's syndrome was made. Our case describes the potentially serious interaction between ICS and oral itraconazole, a treatment very commonly prescribed in patients with ABPA.

Endobronchial chondroid hamartoma of left main bronchus and its bronchoscopic management.

Most tumours of the tracheobronchial tree are malignant. Benign tumours such as hamartoma are infrequent and generally intra-parenchymal. Here we present a case of a 65-year-old male patient who presented with a purely endobronchial lobulated mass lesion in the left main bronchus. This central airway obstruction was managed by a complete endobronchial resection using an electrocautery snare and cryo-recanalisation techniques. A diagnosis of endobronchial chondroid hamartoma was made on histopathological examination. Such endobronchial lesions are rare and constitute less than 2% of all hamartomas.

Doxycycline for the prevention of progression of COVID-19 to severe disease requiring intensive care unit (ICU) admission: A randomized, controlled, open-label, parallel group trial (DOXPREVENT.ICU).

BACKGROUND: After admission to hospital, COVID-19 progresses in a substantial proportion of patients to critical disease that requires intensive care unit (ICU) admission. METHODS: In a pragmatic, non-blinded trial, 387 patients aged 40-90 years were randomised to receive treatment with SoC plus doxycycline (n = 192) or SoC only (n = 195). The primary outcome was the need for ICU admission as judged by the attending physicians. Three types of analyses were carried out for the primary outcome: "Intention to treat" (ITT) based on randomisation; "Per protocol" (PP), excluding patients not treated according to randomisation; and "As treated" (AT), based on actual treatment received. The trial was undertaken in six hospitals in India with high-quality ICU facilities. An online application serving as the electronic case report form was developed to enable screening, randomisation and collection of outcomes data. RESULTS: Adherence to treatment per protocol was 95.1%. Among all 387 participants, 77 (19.9%) developed critical disease needing ICU admission. In all three primary outcome analyses, doxycycline was associated with a relative risk reduction (RRR) and absolute risk reduction (ARR): ITT 31.6% RRR, 7.4% ARR (P = 0.063); PP 40.7% RRR, 9.6% ARR (P = 0.017); AT 43.2% RRR, 10.8% ARR (P = 0.007), with numbers needed to treat (NTT) of 13.4 (ITT), 10.4 (PP), and 9.3 (AT), respectively. Doxycycline was well tolerated with not a single patient stopping treatment due to adverse events. CONCLUSIONS: In hospitalized COVID-19 patients, doxycycline, a safe, inexpensive, and widely available antibiotic with anti-inflammatory properties, reduces the need for ICU admission when added to SoC.

Endobronchial ultrasound guided intracardiac needle aspiration (EBUS-ICNA).

Most cardiac tumours are secondary to metastasis from extracardiac tumours. Obtaining biopsy from intracardiac lesions, especially from the left heart, is challenging, and the conventionally used methods are invasive and involve significant risks such as arrhythmias, tamponade, valvular damage and tumour embolisation. Endobronchial ultrasound (EBUS) is a minimally invasive procedure used to biopsy lymph nodes or mass lesions adjacent to the airways. Its safety and usefulness have been well established. Use of EBUS has expanded to several novel indications over the last few years. Here we report a case of a young woman with suspected metastatic disease to the heart, in whom traditional methods of biopsy had failed to give a diagnosis. EBUS-guided transbronchial intracardiac needle aspiration was safely performed from the left atrial mass lesion to obtain tissue for histopathological diagnosis. A diagnosis of metastatic adenocarcinoma with tumour embolisation to the heart was established.

The clinical experience of macitentan in pulmonary hypertension in Indian cohort: 12-month follow-up.

BACKGROUND: The effectiveness and safety of macitentan, an endothelin-receptor antagonist (ERA) in the treatment of pulmonary arterial hypertension (PAH), has been demonstrated in numerous randomized clinical trials including SERAPHIN, focused on the reduction of morbidity and mortality. OBJECTIVES: Our aim was to demonstrate the clinical and echocardiographic progression using macitentan in Indian patients with PAH. SETTINGS AND DESIGN: It was a retrospective study of 20 patients with multiple etiologies of PAH who had begun macitentan in routine clinical practice from a single center. There were 55% of patients with existing PAH therapies. SUBJECTS AND METHODS: The World Health Organization functional class (WHO-FC), 6-min walking distance, N-terminal prohormone of brain natriuretic peptide level (NT-pro-BNP), and echocardiographic data such as tricuspid annular plane systolic excursion (TAPSE), systolic pulmonary artery pressure (sPAP), and the occurrence of pericardial effusion were collected at baseline and 12-month follow-up. The statistical analysis was performed using SPSS software. RESULTS: Of the 20 PAH patients, 70% were women. The majority were in WHO FC II (50%), while 35% were in FC III and 15% were in FC IV. The mean age was 43.4 years at the start of the therapy with macitentan. After 6 months of macitentan therapy, 85% showed substantial improvement in their FC, each increased its 6-min walking distance test (P < 0.0001), and there was a significant reduction in plasma levels of NT-pro BNP (P < 0.0001). There has also been an improvement in echocardiographic parameters such as TAPSE and sPAP (P < 0.0001). CONCLUSIONS: Our findings indicate that macitentan has been well tolerated and beneficial in Indian patients with PAH and further, future research is required to verify these results.

A multicenter survey study of antifibrotic use for symptomatic patients with post-COVID-19 interstitial lung abnormalities.

Background: Little data exist on antifibrotic drugs for treating symptomatic patients with persistent interstitial lung abnormalities in the postacute phase of coronavirus disease 2019 (COVID-19). Herein, we describe the physician practices of prescribing pirfenidone and nintedanib for these patients and the physician-assessed response. Materials and Methods: This was a multicenter, retrospective survey study of subjects administered pirfenidone or nintedanib for post-COVID-19 interstitial lung abnormalities. Data on the demographic details, comorbidities, abnormalities on the computed tomography (CT) of the chest, treatment, antifibrotic drug use, and physician-assessed response were collected on a standard case record pro forma. We explored physician practices of prescribing antifibrotics (primary objective) and the physician-assessed response (secondary objective). Results: We included 142 subjects (mean age, 55.9 years; 16.2% women) at eight centers. The most common abnormalities on CT chest included ground glass opacities (75.7%), consolidation (49.5%), reticulation (43.9%), and parenchymal bands (16.8%). Of the 5701 patients discharged after hospitalization at six centers, 115 (2.0%) received antifibrotics. The drugs were prescribed an average of 26 days after symptom onset. One hundred and sixteen subjects were administered pirfenidone; 11 (9.5%) received the full dose (2400 mg/day). Thirty subjects were prescribed nintedanib; 23 (76.7%) received the full dose (300 mg/day). Of 76 subjects with available information, 27 (35.6%) and 26 (34.2%) had significant or partial radiologic improvement, respectively, according to the physician's assessment. Conclusions: Antifibrotic agents were administered to a minority of patients discharged after recovery from acute COVID-19 pneumonia. Larger, randomized studies on the efficacy and safety of these agents are required.

Congenital isolated unilateral hypoplasia of the left pulmonary artery: A rare incidental anomaly in an elderly female.

Congenital isolated unilateral hypoplasia of the pulmonary artery (CIUPAH) can have late presentation in the adulthood, mostly diagnosed incidentally, as in our case. They may have symptoms such as exertional dyspnea, recurrent lung infections, and hemoptysis. Although the surgical management is a definitive treatment modality, it depends on the presence of reversible pulmonary hypertension and size of the pulmonary arteries; interventional and medical management can be attempted as a palliative therapy in cases where definitive surgical management is not feasible. We have discussed a rare case of isolated unilateral pulmonary artery hypoplasia which is a congenital anomaly of the lung vasculature without associated congenital heart disease manifested in adulthood.

Bronchoscopic extraction of multiple endobronchial broncholiths in a patient with active pulmonary tuberculosis.

Broncholithiasis is an unusual clinical condition characterized by the presence of calcified or ossified material within the airways. Multiple endobronchial broncholithiasis during active infection with tuberculosis is an extremely uncommon presentation. Bron-choscopy plays an important role in the diagnosis and management of broncholithiasis. Currently, there are no specific guidelines for the management of broncholithiasis. Here, we present a case report where multiple broncholiths were successfully removed in a staged manner via rigid bronchoscopy.

Congenital isolated unilateral agenesis of pulmonary arteries in adults: case series and review.

Congenital, isolated unilateral agenesis of pulmonary arteries (UAPA) has a bimodal clinical presentation. It is either diagnosed in early infancy or during adulthood. Early diagnosis and timely surgical correction at infancy prevent the development of irreversible pulmonary hypertension and enable prolonged survival. Though surgical intervention is a conclusive method of treatment, its outcome depends upon the reversibility of pulmonary hypertension and the adequacy of the pulmonary artery dimension. Adults with UAPA can be asymptomatic (diagnosed incidentally) or symptomatic. They may present clinically with myriads of symptoms like exertional dyspnea, recurrent lung infection, hemoptysis, and atypical chest pain. For cases where definitive surgical treatment is not feasible, interventional and medical management should be carried out as part of palliative therapy. A retrospective analysis of 22 cases of UAPA in adults published in the literature from the years 2017-2020 are presented here, along with our institutional case.

Lobular capillary hemangioma of the trachea - A rare cause of stridor in elderly: A case report with review of literature.

Lobular capillary hemangioma is a rare benign lesion found within the tracheobronchial tree. Patients usually present with recurrent hemoptysis, chronic cough, and rarely, with airway obstruction. We present a case of tracheal lobular capillary hemangioma in a 70-year-old man who presented with stridor and chronic cough. Bronchoscopy showed a 2-cm polypoidal lesion below the vocal cords, which was resected with an electrocautery snare using a rigid bronchoscope. Clinicians should be aware of this entity as one of the differentials for stridor. Bronchoscopic excision of the tumor is feasible and is a minimally invasive therapeutic option for management of these tumors.

Experience with mepolizumab in adults with severe eosinophilic asthma: a case series from India.

Severe asthma can be associated with eosinophilic or allergic phenotypes or both. Eosinophilic inflammation is associated with exacerbations and disease severity due to biological activity of interleukin-5 (IL-5). Patients with severe asthma have reported reduced lung function and poor health-related quality of life (HRQoL) and may require systemic corticosteroids for its management. Thus, treatment targeting IL-5 can help improve quality of life and reduce the use of systemic corticosteroids in severe asthma. Mepolizumab is approved for treating severe eosinophilic asthma as it helps reduce exacerbations, improve lung function and asthma control, and reduce the use of systemic glucocorticoids. This further helps in enhancing HRQoL of these patients. This case series includes four adult patients suffering from severe eosinophilic asthma who were treated with mepolizumab.