Search

Background: The prevalence of nontuberculous mycobacteria pulmonary disease (NTM-PD), particularly caused by Mycobacterium avium complex (MAC), is rising due to improved diagnostics, increased awareness, and more susceptible populations. NTM-PD significantly affects quality of life and imposes substantial economic costs. Understanding its clinical features, risk factors, and treatment challenges is vital for enhancing patient outcomes. Patients and methods: A convenience sample from the University of Connecticut Health Center and Wayne State University involving patients with NTM-PD from 2021 to 2024 was studied retrospectively. Cases were selected to demonstrate typical diagnostic and treatment challenges, followed by a multidisciplinary roundtable discussion to examine patient-centered care strategies. Results: Analysis of six cases pinpointed chronic lung conditions and immunomodulatory therapy as key risk factors. Standard treatment, involving extensive multi-drug regimens, frequently results in poor adherence due to side effects and complex management requirements. The discussions underlined the importance of a customized, interdisciplinary approach to improve treatment effectiveness and patient quality of life. Conclusions: NTM-PD is an escalating public health issue with notable clinical and economic consequences. Managing this disease effectively demands a comprehensive, patient-centered strategy that includes precise diagnosis, flexible treatment plans, and collaborative care. Plain Language Summary: This paper focuses on a type of lung disease caused by nontuberculous mycobacteria (NTM), which are bacteria found in the environment. NTM pulmonary disease has become more common due to better diagnostic methods, increased awareness, and a growing number of people with conditions that make them more vulnerable to infections. This disease can seriously affect a person's quality of life and is challenging to treat because it often requires long and complex antibiotic regimens. The authors, who have expertise in pulmonary diseases and infectious diseases, reviewed the medical records of six patients treated for NTM disease at the University of Connecticut Health Center and Wayne State University between 2021 and 2024. Following the submission of case synopses, the authors engaged in a discussion to explore the challenges of managing NTM infections. The discussion focused on identifying the best practices for diagnosis and treatment, emphasizing a patient-centered approach to care. Patients with preexisting lung conditions or those undergoing certain medical treatments are more susceptible to developing NTM lung disease. The treatment often involved multiple drugs, which posed challenges for patients due to side effects and the complexity of the regimen. The findings underscored the importance of a personalized, collaborative approach in treating NTM lung disease to improve patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Rationale: Nontuberculous mycobacteria (NTM) are prevalent among patients with bronchiectasis. However, the long-term natural history of patients with NTM and bronchiectasis is not well described. Objectives: To assess the impact of NTM on 5-year clinical outcomes and mortality in patients with bronchiectasis. Methods: Patients in the Bronchiectasis and NTM Research Registry with ⩾5 years of follow-up were eligible. Data were collected for all-cause mortality, lung function, exacerbations, hospitalizations, and disease severity. Outcomes were compared between patients with and without NTM at baseline. Mortality was assessed using Cox proportional hazards models and the log-rank test. Measurements and Main Results: In total, 2,634 patients were included: 1,549 (58.8%) with and 1,085 (41.2%) without NTM at baseline. All-cause mortality (95% confidence interval) at Year 5 was 12.1% (10.5%, 13.7%) overall, 12.6% (10.5%, 14.8%) in patients with NTM, and 11.5% (9.0%, 13.9%) in patients without NTM. Independent predictors of 5-year mortality were baseline FEV1 percent predicted, age, hospitalization within 2 years before baseline, body mass index, and sex (all P < 0.01). The probabilities of acquiring NTM or Pseudomonas aeruginosa were approximately 4% and 3% per year, respectively. Spirometry, exacerbations, and hospitalizations were similar, regardless of NTM status, except that annual exacerbations were lower in patients with NTM (P < 0.05). Conclusions: Outcomes, including exacerbations, hospitalizations, rate of loss of lung function, and mortality rate, were similar across 5 years in patients with bronchiectasis with or without NTM. [ABSTRACT FROM AUTHOR]

This letter discusses the impact of tobacco smoking on bronchiectasis, a condition characterized by the widening of the airways in the lungs. The study found that approximately half of patients with bronchiectasis have a history of tobacco smoking, but the development of bronchiectasis is not solely dependent on smoking. The study also found that there were no significant differences in symptoms, treatments, or lung function between smokers and non-smokers with bronchiectasis. However, the presence of chronic obstructive pulmonary disease (COPD) had a more negative impact on outcomes than smoking history alone. The study also revealed an overdiagnosis of COPD, delaying the diagnosis of bronchiectasis. The study suggests the need for accurate phenotyping of patients with bronchiectasis and further research into the underlying mechanisms. [Extracted from the article]

Rationale: CFTR (cystic fibrosis transmembrane conductance regulator) modulator drugs restore function to mutant channels in patients with cystic fibrosis (CF) and lead to improvements in body mass index and lung function. Although it is anticipated that early childhood treatment with CFTR modulators will significantly delay or even prevent the onset of advanced lung disease, lung neutrophils and inflammatory cytokines remain high in patients with CF with established lung disease despite modulator therapy, underscoring the need to identify and ultimately target the sources of this inflammation in CF lungs. Objectives: To determine whether CF lungs, like chronic obstructive pulmonary disease (COPD) lungs, harbor potentially pathogenic stem cell "variants" distinct from the normal p63/Krt5 lung stem cells devoted to alveolar fates, to identify specific variants that might contribute to the inflammatory state of CF lungs, and to assess the impact of CFTR genetic complementation or CFTR modulators on the inflammatory variants identified herein. Methods: Stem cell cloning technology developed to resolve pathogenic stem cell heterogeneity in COPD and idiopathic pulmonary fibrosis lungs was applied to end-stage lungs of patients with CF (three homozygous CFTR:F508D, one CFTR F508D/L1254X; FEV1, 14-30%) undergoing therapeutic lung transplantation. Single-cell--derived clones corresponding to the six stem cell clusters resolved by single-cell RNA sequencing of these libraries were assessed by RNA sequencing and xenografting to monitor inflammation, fibrosis, andmucin secretion. The impact of CFTR activity on these variants after CFTR gene complementation or exposure to CFTRmodulators was assessed by molecular and functional studies. Measurements and Main Results: End-stage CF lungs display a stem cell heterogeneity marked by five predominant variants in addition to the normal lung stem cell, of which three are proinflammatory both at the level of gene expression and their ability to drive neutrophilic inflammation in xenografts in immunodeficient mice. The proinflammatory functions of these three variants were unallayed by genetic or pharmacological restoration of CFTR activity. Conclusions: The emergence of three proinflammatory stem cell variants in CF lungs may contribute to the persistence of lung inflammation in patients with CF with advanced disease undergoing CFTR modulator therapy. [ABSTRACT FROM AUTHOR]