Patients at risk of nontuberculous mycobacterial pulmonary disease who need testing evaluated using a modified Delphi process by European experts.

Background: Identifying patients at risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) is challenging. Delays in NTM-PD identification and management are associated with declining lung function and increased morbidity and mortality. Study design and methods: European NTM-PD experts (n=12) participated in a three-round modified Delphi process to score symptoms and comorbidities potentially associated with NTM-PD as reasons to test for nontuberculous mycobacteria. Results: Experts reached a consensus on the symptoms and comorbidities that should and should not prompt testing for nontuberculous mycobacteria. Requirements for testing were scored as high (mean ≥7), medium (mean ≥4-<7) or low (mean <4). Nontuberculous mycobacteria testing should be undertaken when multiple suggestive symptoms are present simultaneously in all patients except those with cancer (7.3-8.8), or when radiology is indicative of NTM-PD (≥8.9). Symptoms of persistent sputum production, recurrent respiratory infection and haemoptysis should prompt testing for nontuberculous mycobacteria, particularly in those with underlying respiratory diseases. Symptomatic patients with bronchiectasis or previous tuberculosis/NTM-PD or those being prescribed or undergoing long-term macrolide therapy for a respiratory condition should also be tested. Testing is not warranted in patients without an underlying respiratory disorder or in those without a history of respiratory disorders unless presenting with multiple symptoms. Conclusions: Assessing patients' risk of NTM-PD is challenging. This Delphi consensus process provides insight into symptoms and clinical characteristics that should prompt NTM-PD assessment. Timely testing and diagnosis would enable initiation of appropriate management.

Impact of the COVID-19 pandemic on the real-world diagnostic infrastructure for tuberculosis-An ESGMYC collaborative study.

We determined the impact of the COVID-19 pandemic on mycobacterial diagnostic services. 40 laboratories from 22 countries completed an online questionnaire covering the redeployment of the laboratory infrastructure and/or staff for SARS-CoV-2 testing, staff shortages and supply chain disruptions. 28 laboratories reported monthly numbers of samples processed for mycobacterial investigations and monthly numbers of M. tuberculosis complex (MTBC) PCRs performed between October 1st 2018 and October 31st 2020. More than half (23/40) of the participating TB laboratories reported having performed COVID-19 diagnostics in the early phase of the pandemic, in part with negative impact on the mycobacterial service activities. All participating laboratories reported shortages of consumables and laboratory equipment due to supply chain issues. Average monthly sample numbers decreased by 24% between January 2020 and October 2020 compared to pre-pandemic averages. At the end of the study period, most participating laboratories had not returned to pre-pandemic average MTBC PCR throughput.

Airway clearance management in people with bronchiectasis: data from the European Bronchiectasis Registry (EMBARC).

BACKGROUND: International guidelines recommend airway clearance management as one of the important pillars of bronchiectasis treatment. However, the extent to which airway clearance is used for people with bronchiectasis in Europe is unclear. The aim of the study was to identify the use of airway clearance management in patients with bronchiectasis across different countries and factors influencing airway clearance use. METHODS: This was a prospective observational study using data from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) Registry between January 2015 and April 2022. Prespecified options for airway clearance management were recorded, including airway clearance techniques, devices and use of mucoactive drugs. RESULTS: 16 723 people with bronchiectasis from 28 countries were included in the study. The mean age was 67 years (interquartile range 57-74 years, range 18-100 years) and 61% were female. 72% of the participants reported daily sputum expectoration and 52% (95% CI 51-53%) of all participants reported using regular airway clearance management. Active cycle of breathing technique was used by 28% of the participants and airway clearance devices by 16% of participants. The frequency of airway clearance management and techniques used varied significantly between different countries. Participants who used airway clearance management had greater disease severity and worse symptoms, including a higher daily sputum volume, compared to those who did not use it regularly. Mucoactive drugs were also more likely to be used in participants with more severe disease. Access to specialist respiratory physiotherapy was low throughout Europe, but particularly low in Eastern Europe. CONCLUSIONS: Only a half of people with bronchiectasis in Europe use airway clearance management. Use of and access to devices, mucoactive drugs and specialist chest physiotherapy appears to be limited in many European countries.

Nintedanib treatment for bleomycin-induced lung injury - First report.

Although the antineoplastic agent bleomycin is known for more than 50 years, its exact pharmacological and side-effect mechanisms remain incompletely understood. The major limitation of bleomycin therapy is the risk of pulmonary toxicity which can be diverse, and potentially fatal in 10% of patients. The optimal treatment for bleomycin lung toxicity has not been established and no clinical trials have been performed. Here we present first successful case report of nintedanib therapy in a patient with bleomycin-induced lung injury (BILI). The prevention, early diagnosis, and management of bleomycin pulmonary toxicities are essential, clinical trials are needed in this area.

Risk factors and severity of functional impairment in long COVID: a single-center experience in Croatia.

AIM: To determine the frequency of common symptoms in long COVID and their effect on the quality of life, and to determine the factors contributing to a more severe long COVID. METHODS: The study enrolled 266 patients who were either referred to long-COVID outpatient clinic or were inpatients undergoing rehabilitation. The data were collected between December 2020 and May 2021. We evaluated the symptoms experienced during acute and long COVID and comorbidities. Functional status was assessed with Post Covid Functional Status (PCFS). RESULTS: The final sample consisted of 261 patients. After acute COVID-19 period (>4 weeks), almost 80% of patients had impaired functional status. Only 21.5% reported no functional impairment (0 on PCFS scale). A higher PCFS score was associated with female sex (P<0.001) and oxygen therapy requirement during acute disease (P=0.001). However, it was not associated with having a pre-existing lung disease (P=0.749). Disease severity did not pose a risk for developing a more severe long COVID. CONCLUSION: Women were at greater risk for developing greater functional impairment in long COVID, although we have no explanation why. Malignant disease and hypertension also presented a risk factor for greater functional impairment. More studies are warranted to determine if patients with certain lung disease are more susceptible to long COVID.

The role of antibodies in tuberculosis diagnosis, prophylaxis and therapy: a review from the ESGMYC study group.

Tuberculosis (TB) is still responsible for the deaths of >1 million people yearly worldwide, and therefore its correct diagnosis is one of the key components of any TB eradication programme. However, current TB diagnostic tests have many limitations, and improved diagnostic accuracy is urgently needed. To improve the diagnostic performance of traditional serology, a combination of different Mycobacterium tuberculosis (MTB) antigens and different antibody isotypes has been suggested, with some showing promising performance for the diagnosis of active TB. Given the incomplete protection conferred by bacille Calmette-Guérin (BCG) vaccination against adult pulmonary TB, efforts to discover novel TB vaccines are ongoing. Efficacy studies from advanced TB vaccines designed to stimulate cell-mediated immunity failed to show protection, suggesting that they may not be sufficient and warranting the need for other types of immunity. The role of antibodies as tools for TB therapy, TB diagnosis and TB vaccine design is discussed. Finally, we propose that the inclusion of antibody-based TB vaccines in current clinical trials may be advisable to improve protection.

Overview of Symptoms of Ongoing Symptomatic and Post-COVID-19 Patients Who Were Reffered to Pulmonary Rehabilitation - First Single-Centre Experience in Croatia.

BACKGROUND: Coronavirus-2 pandemic has changed the functioning of health systems worldwide. It is not yet fully known which symptoms of the disease are most commonly presented in patients referred for pulmonary rehabilitation. Our aim was to investigate the profile of patients referred for pulmonary rehabilitation; what symptoms they had during the acute phase of the disease and what symptoms were still present at the start of pulmonary rehabilitation. SUBJECTS AND METHODS: Study included ongoing symptomatic and post-COVID patients who attended standard, in person pulmonary rehabilitation program. Patients had COVID-19 disease at least four weeks before attending pulmonary rehabilitation. Patients completed questionnaires of self-reported somatic deficits during acute and post-COVID-19 stage as well as questionnaires regarding their psychological symptoms. Pulmonary function test, expiratory and inspiratory muscle strenght, hand grip strenght and six-minute walk test was performed prior and after pulmonary rehabilitation. RESULTS: Study included 63 patients (32 male, 31 female), with mean age of 52.9 years. During acute COVID-19, majority of patients complained of fatigue, cough, dyspnea, myalgia and headache. More than 85% of patients reported pulmonary deficits during ongoing symptomatic and post-COVID-19 stage. Emotional distress and anxiety levels were significantly elevated in acute stage, while depression, anger and the need for help was not significantly elevated. All reported symptoms were significantly reduced in post-COVID-19 stage. There was statistically significant difference in six-minute walk distance, inspiratory and expiratory muscle strenght and hand grip strenght between first and final testing. CONCLUSIONS: Results of our study are similar with previous studies, the most common symptoms during acute phase were fatigue, cough and dyspnea and fatigue and respiratory problems during ongoing symptomatic and post-COVID stage. Emotional distress diminishes signifiacantly in post-COVID stage. Further larger studies are needed to clarify which acute disease symptoms are predominant in patients referred to pulmonary rehabilitation and cause prolongued discomfort.

Risk factors for nontuberculous mycobacterial pulmonary disease (NTM-PD) in Croatia.

BACKGROUND: The incidence, geographical distribution and clinical relevance of different nontuberculous mycobacteria (NTM) in Croatia are well described. There are few data on the risk factors for developing NTM pulmonary disease (NTM-PD) in this setting. METHODS: We conducted a retrospective cohort study on all Croatian residents with NTM isolated from respiratory samples in the period from 2006 to 2015 with follow-up to 2018. The American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines were used to establish NTM-PD diagnosis. Clinical, radiological and treatment data were collected from hospital records. RESULTS: Risk analysis calculations were made on the 439 isolation episodes that were classified as definitive NTM-PD (n = 137) or no disease (n = 302). Female gender, presence of bronchiectasis, low BMI and long-term systemic corticosteroid treatment were independent risk factors associated with NTM-PD. Hemoptysis and malaise were presenting symptoms independently associated with NTM-PD. Chronic obstructive pulmonary disease (COPD) and low/moderate dose inhaled corticosteroid (ICS) treatment were not associated with NTM-PD. High dose ICS treatment was a significant risk factor for developing NTM-PD (aOR = 4.73, CI 1.69-13.23 p = 0.003). CONCLUSION: The NTM-PD patients in Croatia are similar to those in other published cohorts in terms of their characteristics and risk factors. The significant dose-dependent association between ICS use and NTM-PD adds to the body of evidence suggesting that high dose ICS use is associated with NTM-PD.

Treatment of EGFR positive lung adenocarcinoma in a heart transplanted patient.

Lung cancer incidence in heart transplant patients is higher than in general population and correlates with smoking history. EGFR-mutations are more frequent in adenocarcinoma and among non-smoking women but incidence in solid organ transplanted patients is still not known. We present case of a 65-year-old ex-smoker male with history of heart transplantation and EGFR positive metastatic lung adenocarcinoma. At admission he was in a severe clinical condition and treatment with erlotinib was started. Initially he had good clinical and radiologic response to treatment with only grade 1 side effects.  Data about drug interactions between cyclosporine and erlotinib are insufficient but we have to take this interaction into consideration during treatment because both drugs are substrates and inhibitors of CYP34A. In our case erlotinib was safe and well tolerated drug, there were no relevant toxicity, but close monitoring and dose reduction of cyclosporine was needed.

Neglected disease in mentally ill patients: Major tuberculosis outbreak in a psychiatric hospital.

As tuberculosis incidence decreases, the possibility of overlooking the disease increases, especially in vulnerable populations. We describe here a major tuberculosis outbreak among mentally ill patients in Croatia, focusing on 1 regional hospital where most patients were hospitalized. The outbreak emphasizes the vulnerability of mentally ill patients to tuberculosis infection and the complexity of infection control measures in psychiatric institutions. The awareness of tuberculosis in these settings should be maintained to interrupt prolonged exposure and avoid unnecessary infection.