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Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary microvasculature leading to elevated precapillary pulmonary hypertension. Pulmonary vascular remodeling, a characteristic of PAH, is driven by dysfunctions in the signaling between the pulmonary smooth muscle and endothelial cells with abnormalities that affect cell proliferation and immune dysregulation. Sotatercept, an activin signaling inhibitor, has recently been approved by the US Food and Drug Administration for the treatment of PAH based on two pivotal clinical trials. Evidence-based clinical trials have provided a framework to guide clinicians treating the disease; however, they are not tailored to the individual patient. Often, recommendations from these data are unclear or too general, due to remaining gaps in knowledge. In this edition of "How I Do It," we provide a case-based discussion of common clinical decisions regarding diagnostic testing, choice of first-line agents, escalation of therapy, potential timing of sotatercept, safety awareness, practical use, potential management changes, and the future use of sotatercept in other pulmonary hypertension cohorts. [ABSTRACT FROM AUTHOR]

The association between treatment outcome and the mortality of patients with Mycobacterium avium complex pulmonary disease (MAC-PD) with cavitary lesions is unclear. This article assessed the impact of culture conversion on mortality in patients with cavitary MAC-PD. Is the achievement of sputum culture conversion in patients with MAC-PD with cavitary lesions associated with the prognosis? From 2002 to 2020, a total of 351 patients with cavitary MAC-PD (105 with the fibrocavitary type and 246 with the cavitary nodular bronchiectatic type), who had been treated with a ≥ 6-month macrolide-containing regimen at a tertiary referral center in South Korea, were retrospectively enrolled in this study. All-cause mortality during the follow-up period was analyzed based on culture conversion at the time of treatment completion. The cohort had a median treatment duration of 14.7 months (interquartile range [IQR], 13.4-16.8 months). Of the 351 patients, 69.8% (245 of 351) achieved culture conversion, and 30.2% (106 of 351) did not. The median follow-up was 4.4 years (IQR, 2.3-8.3 years) in patients with culture conversion and 3.1 years (IQR, 2.1-4.8 years) in those without. For the patients with and without culture conversion, all-cause mortality was 5.3% vs 35.8% (P <.001), and the 5-year cumulative mortality was 20.0% vs 38.4%, respectively. Cox analysis found that a lack of culture conversion was significantly associated with higher mortality (adjusted hazard ratio, 5.73; 95% CI, 2.86-11.50). Moreover, the 2-year landmark analysis revealed a distinct impact of treatment outcome on mortality. The mortality rate of patients with cavitary MAC-PD who did not achieve culture conversion was significantly higher than that of those with culture conversion. [ABSTRACT FROM AUTHOR]

An 81-year-old man who currently smokes with a 30-pack-year history presented with involuntary rhythmic motion of his right hand that had started insidiously and progressively worsened over the past 5 months. His medical history included hypertension and dyslipidemia. He did not have a prior history of pulmonary disease and currently denied any shortness of breath or cough. He did however report an unintentional weigh loss of 5 kg within the past few months. [ABSTRACT FROM AUTHOR]

A 62-year-old woman came to our hospital with worsening cough and dyspnea over the preceding week, during which time she had been treated with azithromycin and prednisone for suspected pneumonia. She had no fever, chills, or sweats, but her cough had become productive of clear to blood-tinged phlegm during the interval. Medical history was significant for insulin-dependent diabetes mellitus and OSA. She had quit smoking 44 years earlier and had no history of lung disease. She was a bank teller residing in southeastern Minnesota and described no relevant inhalational or environmental exposures, drug use, aspiration, or travels preceding her illness. [ABSTRACT FROM AUTHOR]

Community advisory boards (CABs) are increasingly recognized as a means of incorporating patient experience into clinical practice and research. The power of CABs is derived from engaging with community members as equals throughout the research process. Despite this, little is known of community member experience and views on best practices for running a CAB in a rare pulmonary disease. What are CAB members' views on the best practices for CAB formation and maintenance in a rare pulmonary disease? In August 2021, we formed the Cleveland Clinic Sarcoidosis Health Partners (CC-HP) as a CAB to direct research and clinic improvement initiatives at a quaternary sarcoidosis center. We collaboratively evaluated our process for formation and maintenance of the CC-HP with the patient members of the group. Through the series of reflection/debriefing discussions, CAB patient members developed a consensus account of salient obstacles and facilitators of forming and maintaining a CAB in a rare pulmonary disease. Clinician and community members of the CC-HP found published guidelines to be an effective tool for structuring formation of a CAB in a rare pulmonary disease. Facilitators included a dedicated coordinator, collaborative development of projects, and a focus on improving clinical care. Obstacles to CAB functioning were formal structure, focus on projects with academic merit but no immediate impact to patients, and overreliance on digital resources. By centering our evaluation of our CAB on community member experience, we were able to both identify facilitators and impediments to CAB as well as improve our own processes. [ABSTRACT FROM AUTHOR]

Lung transplantation is a lifesaving intervention for people with advanced lung disease, but it is costly and resource-intensive. To investigate the cost-effectiveness of lung transplantation as a treatment option in pulmonary disease, we must understand costs attributable to end-of-life hospitalizations for end-stage lung disease. What are the costs associated with end-of-life hospitalizations for people with pulmonary disease, and how have these trends changed over time? Adults aged 18 to 74 years with hospitalization data in the Cost and Utilization Project National Inpatient Sample data from 2009 to 2019 with a pulmonary disease admission were included in this analysis. Those with a history of lung transplantation were excluded. International Classification of Diseases codes were used to identify pulmonary disease admissions, complications, and procedures and interventions. Total charges were calculated for hospitalizations and stratified by patient status at time of discharge. Trends in charges over time were assessed by demographic and hospital factors. One hundred nine thousand nine hundred twenty-four (4.1%) hospital admissions for pulmonary disease resulted in in-hospital mortality. Those with obstructive lung disease accounted for 94.1% of hospitalizations and 88.1% cases of in-hospital mortality. Estimated costs for end-of-life hospitalizations were $29,981 on average with wide variation in cost by diagnosis and procedure utilization. Inpatient costs were highest for younger people who received more procedures. Among the most expensive admissions, mechanical ventilation accounted for the greatest proportion of interventions. Significant increases in the use of mechanical ventilation, extracorporeal membrane oxygenation, and dialysis occurred over the time period. The rate of hospital transfers increased with a proportionately greater increase across admissions resulting in in-hospital mortality. Costs accrued during end-of-life hospitalizations vary across people but represent a significant health care cost that can be averted for selected people who undergo lung transplantation. These costs should be considered in studies of cost-effectiveness in lung transplantation. [Display omitted] [ABSTRACT FROM AUTHOR]

This novel report presents the first known case, to our knowledge, of a 16-year-old male patient who experienced intraventricular thrombosis and pulmonary embolism after a Nuss procedure for pectus excavatum, attributed to chronic bar displacement. Two years after the operation, the patient experienced post-exercise cough and hemoptysis, which led to his admission. Imaging revealed pulmonary embolism, thrombosis in the right ventricular outflow tract, and lung infiltrative lesions. We hypothesize that the chronic bar displacement led to its embedment in the right ventricle, resulting in thrombus formation, which subsequently contributed to partial pulmonary embolism. Surgery revealed the bars' intrusion into the right ventricle and lung. This case highlights the risk of severe complications from bar displacement in the Nuss procedure, which necessitates long-term follow-up evaluation, caution against strenuous activities after surgery, and use of thoracoscopic guidance during bar implantation and removal. It underscores the importance of vigilant evaluation for late-stage complications in patients with respiratory distress or thrombosis after a Nuss procedure. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria are environmental organisms that are increasingly causing chronic and debilitating pulmonary infections, of which Mycobacterium avium complex (MAC) is the most common pathogen. MAC pulmonary disease (MAC-PD) is often difficult to treat, often requiring long-term multidrug antibiotic therapy. Is there an association between various guideline-based three-drug therapy (GBT) regimens and (1) therapy-associated adverse events or (2) regimen change/discontinuation, within 12 months of therapy initiation? In a retrospective cohort study, we examined tolerability outcomes of GBT regimens for MAC-PD in 4,626 US Medicare beneficiaries with bronchiectasis, who were prescribed a GBT as initial antibiotic treatment for presumed MAC-PD during 2006 to 2014. Using multivariable Cox proportional hazard regression, we estimated adjusted hazard ratios (aHRs) to compare the risk of adverse events and regimen change/discontinuations within 12 months of therapy initiation in various GBT regimens. The cohort had a mean age ± SD of 77.9 ± 6.1 years at treatment start, were mostly female (77.7%), and were mostly non-Hispanic White (87.2%). The risk of regimen change/discontinuation within 12 months of therapy was higher for clarithromycin-based regimens than azithromycin-based regimens (aHR, 1.12; 95% CI, 1.04-1.20 with rifampin; aHR, 1.11; 95% CI, 0.93-1.32 with rifabutin as the companion rifamycin), and for rifabutin-containing regimens than rifampin-containing regimens (aHR, 1.49; 95% CI, 1.33-1.68 with azithromycin; aHR, 1.47; 95% CI, 1.27-1.70 with clarithromycin as the companion macrolide). The aHR comparing regimen change/discontinuation with clarithromycin-ethambutol-rifabutin and azithromycin-ethambutol-rifampin was 1.64 (95% CI, 1.43-1.64). Overall, an azithromycin-based regimen was less likely to be changed or discontinued than a clarithromycin-based regimen, and a rifampin-containing regimen was less likely to be changed or discontinued than a rifabutin-containing regimen within 12 months of therapy start. Our work provides a population-based assessment on the tolerability of multidrug antibiotic regimens used for the treatment of MAC-PD. [Display omitted] [ABSTRACT FROM AUTHOR]

Results of retrospective studies have suggested clofazimine as an alternative for rifampicin in the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). Is a treatment regimen consisting of clofazimine-ethambutol-macrolide noninferior to the standard treatment regimen (rifampicin-ethambutol-macrolide) in the treatment of MAC-PD? In this single-center, nonanonymized clinical trial, adult patients with MAC-PD were randomly assigned in a 1:1 ratio to receive rifampicin or clofazimine as adjuncts to an ethambutol-macrolide regimen. The primary outcome was sputum culture conversion following 6 months of treatment. Forty patients were assigned to receive either rifampicin (n = 19) or clofazimine (n = 21) in addition to ethambutol and a macrolide. Following 6 months of treatment, both arms showed similar percentages of sputum culture conversion based on an intention-to-treat analysis: 58% (11 of 19) for rifampicin and 62% (13 of 21) for clofazimine. Study discontinuation, mainly due to adverse events, was equal in both arms (26% vs 33%). Based on an on-treatment analysis, sputum culture conversion following 6 months of treatment was 79% in both groups. In the clofazimine arm, diarrhea was more prevalent (76% vs 37%; P =.012), while arthralgia was more frequent in the rifampicin arm (37% vs 5%; P =.011). No difference in the frequency of corrected QT interval prolongation was seen between groups. A clofazimine-ethambutol-macrolide regimen showed similar results to the standard rifampicin-ethambutol-macrolide regimen and should be considered in the treatment of MAC-PD. The frequency of adverse events was similar in both arms, but their nature was different. Individual patient characteristics and possible drug-drug interactions should be taken into consideration when choosing an antibiotic regimen for MAC-PD. EudraCT; No.: 2015-003786-28; URL: https://eudract.ema.europa.eu [Display omitted] [ABSTRACT FROM AUTHOR]

A 52-year-old woman with no significant medical history was referred to our hospital for expedited workup of progressive dysarthria and ataxia over the past year. Prior CT angiography of the head and neck showed no relevant neurologic findings but did reveal miliary lesions in the lung apices, which was later confirmed via dedicated CT chest scan (Fig 1). Review of systems was negative for any respiratory, constitutional, or rheumatologic symptoms, except for new xanthelasma-like lesions over her forehead. She previously had smoked with 20 pack-years and had no TB risk factors. MRI of the face showed a 21-mm mass within the left external temporal fascia. MRI of the head showed diffuse leptomeningeal enhancement, right frontal lobe enhancement, and cerebellar and brainstem T2/fluid-attenuated inversion recovery hyperintensity, which prompted her admission to hospital. [ABSTRACT FROM AUTHOR]

The clinical course of nontuberculous mycobacterial pulmonary disease (NTM-PD) can be variable and difficult to predict. Recently, the BACES score was developed as a tool to predict all-cause mortality in patients with NTM-PD. This score is calculated based on five patient characteristics (BMI, age, cavity, erythrocyte sedimentation rate, and sex), and higher scores portend worse prognosis. Although the BACES score has been validated in a cohort of South Korean patients, it has not yet been validated in other settings or ethnic groups. How well does the BACES mortality score perform in a cohort of Canadian patients with NTM-PD? We performed a single-center retrospective chart review. Patients who were seen between July 2003 and June 2021 were eligible for inclusion if they met guideline-based diagnostic criteria for NTM-PD and were excluded if any component of the BACES score was missing. To assess the model's discriminatory performance, we compared Kaplan-Meier curves between risk groups and calculated Harrell's C index. To assess calibration, we used a graphical calibration curve. The cohort included 435 patients with a median follow-up of 5.8 years. The median age was 64 years and 74% were female. Based on the BACES scores, patients were classified into three risk groups: low, moderate, or high. Survival curves showed clear separation of the risk groups. Harrell's C index was 0.733 in the study cohort, indicating moderate to good discriminatory performance, although this was lower than the value reported in the derivation cohort (0.812). The graphical calibration curve showed a tendency of the BACES model to underpredict mortality. The BACES model was evaluated in a multicultural cohort of Canadian patients and demonstrated good discriminatory performance but suboptimal calibration, which may be due to population differences, the use of dichotomized variables in model construction, or both. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with left-sided heart and lung diseases are most commonly easily discriminated and treated accordingly. With the changing epidemiology of PAH, however, a growing proportion of patients at the time of diagnosis present with comorbidities of varying severity. In addition to classical PAH, two distinct phenotypes have emerged: a heart failure with preserved ejection fraction-like phenotype and a lung phenotype. Importantly, the evidence supporting the currently proposed treatment algorithm for PAH has been generated mainly from PAH trials in which patients with cardiopulmonary comorbidities have been underrepresented or excluded. As a consequence, the best therapeutic approach for patients with common PAH with cardiopulmonary comorbidities remains largely unknown and requires further investigation. The present article reviews the relevant literature on the topic and describes the authors' views on the current therapeutic approach for these patients. [ABSTRACT FROM AUTHOR]

An 8-year-old girl presented with a 34-day history of cough, fatigue, and impaired exercise tolerance. She experienced cyanosis on exertion but denied fever, hemoptysis, hematuria, or seizures. Her perinatal and family histories were unremarkable, and she had no history of exposure to TB. A chest radiogram from a local clinic showed diffuse pulmonary lesions. Tuberculin skin test, interferon-γ release assay, and HIV antibody test results were all negative. Immunoglobulin levels and lymphocyte subsets were normal. The patient did not respond to IV azithromycin for 1 week for community-acquired pneumonia. She was transferred to our hospital because of progressive respiratory distress and hypoxemia. [ABSTRACT FROM AUTHOR]

No studies have reported therapies for the treatment of patients with refractory Mycobacterium abscessus pulmonary disease (MAB-PD). We implemented intermittent multidrug IV therapy (IMIT) through repeated hospitalizations for patients with MAB-PD who were refractory to antibiotics for more than 12 months. What are the effects of IMIT on patients with refractory MAB-PD? The IV antibiotics administered for IMIT included amikacin, imipenem, and tigecycline, and the outcomes for 36 patients who underwent IMIT for refractory MAB-PD were evaluated. Patients were repeatedly hospitalized and administered IMIT on recurrent symptoms or radiographic evidence of deterioration, while maintaining oral/inhaled antibiotics. Of the 36 patients, 26 (72%) had M abscessus subspecies abscessus (herein, M abscessus)-PD, and 10 (28%) had M abscessus subspecies massiliense (herein, M massiliense)-PD. The median number of hospitalizations for IMIT was two (interquartile range, 1-3) for patients with M abscessus -PD and one (interquartile range, 1-2) for patients with M massiliense -PD. At least one negative culture result and culture conversion were observed in 62% and 12% of patients with M abscessus -PD, and in 80% and 60% of patients with M massiliense -PD, respectively. Symptomatic improvement was observed in all patients, and radiologic improvement, including cavity amelioration or no deterioration, was observed in 42% and 70% of patients with M abscessus -PD and with M massiliense -PD, respectively. No resistance to clarithromycin or amikacin was acquired. IMIT with intermittent hospitalization can be a beneficial palliative treatment for patients with refractory MAB-PD. This therapy alleviated symptoms, slowed radiologic progression, and reduced the bacterial burden in some patients. However, radiologic and microbiological responses to IMIT were more apparent in M massiliense -PD than in M abscessus -PD. [ABSTRACT FROM AUTHOR]

A 20-year-old patient with cystic fibrosis (CF) complicated by pansinusitis, pancreatic insufficiency, and diabetes presented to the local ED after an episode of large-volume hemoptysis at home. At baseline, she had advanced lung disease (FEV 1 , 0.97 L; 31% predicted) and upper lobe-predominant fibrocavitary changes. She was intermittently followed at a regional lung transplant center. She was previously evaluated for transplant but was not listed at the time of this presentation because of nontuberculous mycobacteria infection. She had never used tobacco, without reports of recreational inhaled drug use. Her mother had CF, and one of her brothers died in 2018 at age 24 of respiratory failure resulting from the disease. [ABSTRACT FROM AUTHOR]

Pulmonary involvement is the leading cause of death in systemic sclerosis (SSc) and may manifest as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), or in combination of both (ILD with pulmonary hypertension [ILD-PH]). The aim of this analysis was to determine prevalence, clinical characteristics, and survival of these different forms within the registry of the German Network for Systemic Sclerosis. Does SSc-associated ILD-PH or ILD without PH affect survival differently, and are there any risk factors that have an additional impact? Clinical data of 5,831 patients with SSc were collected in the German Network for Systemic Sclerosis registry. Kaplan-Meier estimates were used to compare overall survival in patients with SSc-associated ILD-PH and ILD without PH with patients without pulmonary involvement and those with PAH. The Cox proportional hazard model was used to analyze the influence of pulmonary involvement and other potential predictors on patient survival. Clinical data of 3,257 patients with a mean follow-up time of 3.45 ± 1.63 years have been included in our analysis. At baseline, ILD was present in 34.5%, whereas PH without ILD had a lower prevalence with 4.5%. At the end of follow-up, 47.6% of patients with SSc had ILD, 15.2% had ILD-PH, and 6.5% had PAH. ILD was more frequent in the diffuse cutaneous form (57.3%), whereas PAH did not differ significantly between SSc subtypes. Significant differences in baseline characteristics between PAH vs ILD-PH vs ILD without PH were found for age at diagnosis, sex, SSc subsets, antibody status, FVC, diffusing capacity of the lung for carbon monoxide, and therapy. Overall survival at 5 years was 96.4% for patients without pulmonary involvement and differed significantly between patients with ILD without PH, PAH, and being worst in patients with ILD-PH. Female sex (hazard ratio [HR], 0.3), higher BMI (HR, 0.9), and higher diffusing capacity of the lung for carbon monoxide values (HR, 0.98) were associated with a lower mortality risk. ILD is the most prevalent pulmonary involvement in SSc, whereas the combination of ILD and PH is associated with the most detrimental survival. [Display omitted] [ABSTRACT FROM AUTHOR]

Subpleural micronodules and interlobular septal thickening are common CT scan findings in TB pleural effusion. These CT scan features could help us differentiate between TB pleural effusion and nonTB empyema. Does the frequency of subpleural micronodules and interlobular septal thickening correlate with the presence of pleural effusion in patients with pulmonary TB? CT scan findings of pulmonary TB, micronodules and their distribution (peribronchovascular, septal, subpleural, centrilobular, and random), large opacity (consolidation/macronodule), cavitation, tree-in-buds, bronchovascular bundle thickening, interlobular septal thickening, lymphadenopathy, and pleural effusion were retrospectively analyzed. Patients were divided into two groups according to the presence of pleural effusion. Clinicoradiologic findings of the two groups were then analyzed. We presented Benjamini-Hochberg critical value for multiple testing correction of CT scan findings, with a false discovery rate of 0.05. Of a total of 338 consecutive patients diagnosed with pulmonary TB who underwent CT scans, 60 were excluded because of coexisting pulmonary diseases. The frequency of subpleural nodules (47/68, 69% in pulmonary TB with pleural effusion vs 30/210, 14% in pulmonary TB without effusion, P <.001, Benjamini-Hochberg [B-H] critical value = 0.0036) and interlobular septal thickening (55/68, 81% vs 134/210, 64%, P =.009, B-H critical value = 0.0107) was significantly higher in the group of patients with pulmonary TB with pleural effusion than in the group without pleural effusion. In contrast, tree-in-buds (20/68, 29% vs 101/210, 48%, P =.007, B-H critical value = 0.0071) were less frequently seen in patients with pulmonary TB with pleural effusion. Subpleural nodules and septal thickening were more common in pulmonary TB patients with pleural effusion than in those without pleural effusion. TB involvement of the lymphatics in the peripheral interstitium could be associated with the development of pleural effusion. [ABSTRACT FROM AUTHOR]

A 56-year-old man with a medical history of diabetes, no prior lung disease, and no tobacco exposure presented with exhaustion and a nonproductive cough 7 days after working in an old farmhouse in Vermont. His friend who worked with him exhibited similar symptoms. He was treated as an outpatient with doxycycline; however, his clinical condition deteriorated and necessitated hospitalization and subsequent intubation. [ABSTRACT FROM AUTHOR]

Morbidity and mortality from nontuberculous mycobacterial pulmonary disease (NTM-PD) are increasing. Mycobacterium avium complex (MAC) is the most common cause of NTM-PD. Microbiological outcomes are widely used as the primary end point of antimicrobial treatment, but their long-term impact on prognosis is uncertain. Do patients who achieve microbiological cure at the end of treatment have longer survival than those who do not? We retrospectively analyzed adult patients who met the diagnostic criteria for NTM-PD, were infected with MAC species, and were treated with a macrolide-based regimen for ≥ 12 months per guidelines between January 2008 and May 2021 at a tertiary referral center. Mycobacterial culture was performed during antimicrobial treatment to assess the microbiological outcome. Patients with three or more consecutive negative cultures collected ≥ 4 weeks apart and no positive cultures until treatment completion were considered to have achieved microbiological cure. To assess the impact of microbiological cure on all-cause mortality, we performed multivariable Cox proportional hazards regression analysis adjusted for age, sex, BMI, presence of cavitary lesions, erythrocyte sedimentation rate, and underlying comorbid conditions. Among 382 patients enrolled, 236 (61.8%) achieved microbiological cure at completion of treatment. These patients were younger, had lower erythrocyte sedimentation rates, were less likely to use four or more drugs, and had shorter treatment duration than those who failed to achieve microbiological cure. During a median follow-up of 3.2 (first quartile to third quartile, 1.4-5.4) years after treatment completion, 53 patients died. Microbiological cure was significantly associated with reduced mortality after adjustment for major clinical factors (adjusted hazard ratio, 0.52; 95% CI, 0.28-0.94). The association between microbiological cure and mortality was maintained in a sensitivity analysis that included all patients treated < 12 months. Microbiological cure at completion of treatment is associated with longer survival in patients with MAC-PD. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is widely underdiagnosed, and certain patient groups, such as those with underlying respiratory diseases, are at increased risk of developing the disease. Understanding patients at risk is essential to allow for prompt testing and diagnosis and appropriate management to prevent disease progression. What are the risk factors for NTM-PD that should prompt a physician to consider NTM testing and diagnosis? Electronic searches of PubMed and EMBASE were conducted in July 2021 for the period 2011-2021. Inclusion criteria were studies of patients with NTM-PD with associated risk factors. Data were extracted and assessed using the Newcastle-Ottawa Scale. Data analysis was conducted using the R-based "meta" package. Only studies that reported association outcomes for cases with NTM-PD compared with control participants (healthy populations or participants without NTM-PD) were considered for the meta-analysis. Of the 9,530 searched publications, 99 met the criteria for the study. Of these, 24 formally reported an association between possible risk factors and the presence of NTM-PD against a control population and were included in the meta-analysis. Comorbid respiratory disease was associated with a significant increase in the OR for NTM-PD (bronchiectasis [OR, 21.43; 95% CI, 5.90-77.82], history of TB [OR, 12.69; 95% CI, 2.39-67.26], interstitial lung disease [OR, 6.39; 95% CI, 2.65-15.37], COPD [OR, 6.63; 95% CI, 4.57-9.63], and asthma [OR, 4.15; 95% CI, 2.81-6.14]). Other factors noted to be associated with an increased risk of NTM-PD were the use of inhaled corticosteroids (OR 4.46; 95% CI, 2.13-9.35), solid tumors (OR, 4.66; 95% CI, 1.04-20.94) and the presence of pneumonia (OR, 5.54; 95% CI, 2.72-11.26). The greatest risk for NTM-PD is conferred by comorbid respiratory diseases such as bronchiectasis. These findings could help with identification of patient populations at risk for NTM-PD to drive prompt testing and appropriate initiation of therapy. [ABSTRACT FROM AUTHOR]

CT scan imaging provides high-resolution images of the lungs in patients with chronic respiratory diseases. Extensive research over the last several decades has focused on developing novel quantitative CT scan airway measurements that reflect abnormal airway structure. Despite many observational studies demonstrating that associations between CT scan airway measurements and clinically important outcomes such as morbidity, mortality, and lung function decline, few quantitative CT scan measurements are applied in clinical practice. This article provides an overview of the relevant methodologic considerations for implementing quantitative CT scan airway analyses and provides a review of the scientific literature involving quantitative CT scan airway measurements used in clinical or randomized trials and observational studies of humans. We also discuss emerging evidence for the clinical usefulness of quantitative CT scan imaging of the airways and discuss what is required to bridge the gap between research and clinical application. CT scan airway measurements continue to improve our understanding of disease pathophysiologic features, diagnosis, and outcomes. However, a literature review revealed a need for studies evaluating clinical benefit when quantitative CT scan imaging is applied in the clinical setting. Technical standards for quantitative CT scan imaging of the airways and high-quality evidence of clinical benefit from management guided by quantitative CT scan imaging of the airways are required. [ABSTRACT FROM AUTHOR]

Mycobacterium abscessus is the second most common nontuberculous mycobacterium respiratory pathogen and shows in vitro resistance to nearly all oral antimicrobials. M abscessus treatment success is low in the presence of macrolide resistance. Does treatment with amikacin liposome inhalation suspension (ALIS) improve culture conversion in patients with M abscessus pulmonary disease who are treatment naive or who have treatment-refractory disease? In an open-label protocol, patients were given ALIS (590 mg) added to background multidrug therapy for 12 months. The primary outcome was sputum culture conversion defined as three consecutive monthly sputum cultures showing negative results. The secondary end point included development of amikacin resistance. Of 33 patients (36 isolates) who started ALIS with a mean age of 64 years (range, 14-81 years), 24 patients (73%) were female, 10 patients (30%) had cystic fibrosis, and nine patients (27%) had cavitary disease. Three patients (9%) could not be evaluated for the microbiologic end point because of early withdrawal. All pretreatment isolates were amikacin susceptible and only six isolates (17%) were macrolide susceptible. Eleven patients (33%) were given parenteral antibiotics. Twelve patients (40%) received clofazimine with or without azithromycin as companion therapy. Fifteen patients (50%) with evaluable longitudinal microbiologic data demonstrated culture conversion, and 10 patients (67%) sustained conversion through month 12. Six of the 33 patients (18%) demonstrated mutational amikacin resistance. All were patients using clofazimine or clofazimine plus azithromycin as companion medication(s). Few serious adverse events occurred for ALIS users; however, reduction of dosing to three times weekly was common (52%). In a cohort of patients primarily with macrolide-resistant M abscessus , one-half of the patients using ALIS showed sputum culture conversion to negative findings. The emergence of mutational amikacin resistance was not uncommon and occurred with the use of clofazimine monotherapy. ClinicalTrials.gov; No.: NCT03038178; URL: www.clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Even though patients with pulmonary arterial hypertension have multiple therapeutic options, the disease can be refractory despite appropriate management. In patients with end-stage pulmonary arterial hypertension, lung transplantation has the potential both to extend survival and improve health-related quality of life. Pulmonary arterial hypertension is the only major diagnostic indication for transplantation that is not a parenchymal pulmonary process, and thus the care of these patients is unique. This review focuses on the complexities of lung transplantation for patients with pulmonary arterial hypertension, presents the updated referral and listing criteria, and discusses the inequities in the organ allocation process that impact this disease group and the strategies to optimize outcomes for patients with pulmonary arterial hypertension who require lung transplantation. Lung transplantation is an effective and lifesaving therapy for patients with end-stage lung disease. Sadly, patients with pulmonary arterial hypertension face many challenges as it relates to transplantation including higher perioperative risks, inequities in the allocation system, and less favorable long-term outcomes. This review covers the complexities of transplantation in patients with pulmonary vascular disease. [ABSTRACT FROM AUTHOR]

Climate change adversely impacts global health. Increasingly, temperature variability, inclement weather, declining air quality, and growing food and clean water supply insecurities threaten human health. Earth's temperature is projected to increase up to 6.4 °C by the end of the 21st century, exacerbating the threat. Public and health care professionals, including pulmonologists, perceive the detrimental effects of climate change and air pollution and support efforts to mitigate its effects. In fact, evidence is strong that premature cardiopulmonary death is associated with air pollution exposure via inhalation through the respiratory system, which functions as a portal of entry. However, little guidance is available for pulmonologists in recognizing the effects of climate change and air pollution on the diverse range of pulmonary disorders. To educate and mitigate risk for patients competently, pulmonologists must be armed with evidence-based findings of the impact of climate change and air pollution on specific pulmonary diseases. Our goal is to provide pulmonologists with the background and tools to improve patients' health and to prevent adverse outcomes despite climate change-imposed threats. In this review, we detail current evidence of climate change and air pollution impact on a diverse range of pulmonary disorders. Knowledge enables a proactive and individualized approach toward prevention strategies for patients, rather than merely treating ailments reactively. [ABSTRACT FROM AUTHOR]

A 54-year-old woman with systemic lupus erythematosus with associated interstitial lung disease (ILD) presented to the lung transplant clinic for assessment of candidacy for transplantation. She was initially diagnosed with ILD based on clinical and radiographic features (never underwent lung biopsy). In addition, she had associated mixed group I/III pulmonary arterial hypertension. The patient had no family history of pulmonary disease and had never used tobacco and did not have a history of illicit drug use. She was maintained on systemic immunosuppression with hydroxychloroquine, mycophenolate mofetil, and nintedanib for ILD as well as inhaled treprostinil, sildenafil, and macitentan for pulmonary arterial hypertension. Given her progressive symptoms on maximal medical therapy, she was referred for consideration to undergo lung transplantation. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria (NTM), predominately Mycobacterium avium complex (MAC), cause chronic pulmonary disease. Improvements in symptoms and health-related quality of life (HRQoL) are important treatment outcomes, but no validated patient-reported outcome (PRO) measure exists. What are the validity and responsiveness of the Quality of Life-Bronchiectasis (QOL-B) questionnaire respiratory symptoms scale and key HRQoL measures during the first 6 months of MAC pulmonary disease (MAC-PD) treatment? Comparison of Two- vs Three-antibiotic Therapy for Pulmonary Mycobacterium Avium Complex Disease (MAC2v3) is an ongoing randomized, multisite pragmatic clinical trial. Patients with MAC-PD were randomized to azithromycin-based two-drug or three-drug therapy; treatment groups were combined for this analysis. PROs were measured at baseline, 3 months, and 6 months. The QOL-B respiratory symptoms, vitality, physical functioning, health perceptions, and NTM symptom domain scores (on a scale of 0-100, with 100 being best) were analyzed separately. We performed psychometric and descriptive analyses in the population enrolled as of the time of analysis and calculated the minimal important difference (MID) using distribution-based methods. Finally, we evaluated responsiveness using paired t tests and latent growth curve analysis in the subset with longitudinal surveys completed by the time of analysis. The baseline population included 228 patients, of whom 144 had completed longitudinal surveys. Patients predominately were female (82%) and had bronchiectasis (88%); 50% were 70 years of age or older. The respiratory symptoms domain showed good psychometric properties (no floor or ceiling effects; Cronbach's α, 0.85) and an MID of 6.4 to 6.9. Vitality and health perceptions domain scores performed similarly. Respiratory symptoms domain scores improved by 7.8 points (P <.0001) and 7.5 points (P <.0001), and the physical functioning domain score improved by 4.6 points (P <.003) and 4.2 points (P =.01) at 3 and 6 months, respectively. Latent growth curve analysis confirmed a nonlinear, statistically significant improvement in respiratory symptoms and physical functioning domain scores by 3 months. The QOL-B respiratory symptoms and physical functioning scales exhibited good psychometric properties in patients with MAC-PD. Respiratory symptoms scores improved beyond the MID by 3 months after treatment initiation. ClinicalTrials.gov; No.: NCT03672630; URL: www.clinicaltrials.gov [ABSTRACT FROM AUTHOR]

There is expansive literature documenting the presence of health disparities, but there are disproportionately few studies describing interventions to reduce disparity. In this narrative review, we categorize interventions to reduce health disparity in pulmonary disease within the US health care system to support future initiatives to reduce disparity. We identified 211 articles describing interventions to reduce disparity in pulmonary disease related to race, income, or sex. We grouped the studies into the following four categories: biologic, educational, behavioral, and structural. We identified the following five main themes: (1) there were few interventional trials compared with the breadth of studies describing health disparities, and trials involving patients with asthma who were Black, low income, and living in an urban setting were overrepresented; (2) race or socioeconomic status was not an effective marker of individual pharmacologic treatment response; (3) telehealth enabled scaling of care, but more work is needed to understand how to leverage telehealth to improve outcomes in marginalized communities; (4) future interventions must explicitly target societal drivers of disparity, rather than focusing on individual behavior alone; and (5) individual interventions will only be maximally effective when specifically tailored to local needs. Much work has been done to catalog health disparities in pulmonary disease. Notable gaps in the identified literature include few interventional trials, the need for research in diseases outside of asthma, the need for high quality effectiveness trials, and an understanding of how to implement proven interventions balancing fidelity to the original protocol and the need to adapt to local barriers to care. [ABSTRACT FROM AUTHOR]

The National Board for Respiratory Care credentials general respiratory therapists and therapists specializing in pulmonary function testing, neonatal/pediatrics, sleep, and adult critical care. A sponsor of the NBRC requested a new specialty certification program. The request came with the intent to serve a candidate population from multidisciplinary backgrounds (eg, nurse, nurse practitioner, physician assistant) in addition to respiratory therapists. This article describes the policy that governed the response along with details about two evaluations: a viability study and a personnel study. The research question for the viability study was as follows: Is a new pulmonary disease educator certification program desirable and feasible? After an affirmative outcome from the viability study indicated interest in a new certification program, the research question for the personnel study was as follows: Were there enough potential candidates from multidisciplinary backgrounds to support a new program that would certify pulmonary disease educators? Access to 10 databases was secured to solicit personnel from multidisciplinary backgrounds, netting up to 240,000 potential survey respondents. After pilot testing, one survey was distributed to those with managerial/supervisory relationships with pulmonary disease educators; 407 such personnel responded. A second survey was simultaneously distributed to those directly working in the pulmonary disease educator role; 3,095 responded. Results from both surveys, including the limitations, were summarized for the NBRC, which decided against continued development of the program. A pulmonary disease educator certification program was subjectively desirable and feasible; however, there did not objectively seem to be enough potential candidates to support the program. [ABSTRACT FROM AUTHOR]

Although interstitial lung disease (ILD) is a leading cause of morbidity and mortality in patients with inflammatory myopathies, the current definition and diagnostic criteria of autoimmune myositis remain inadequate to capture the large proportion of patients with lung-dominant disease. As a result, these patients present unique diagnostic and treatment challenges for even the most experienced clinicians. This article highlights the emerging role of autoantibodies in the diagnosis, classification, and management of patients with ILD. We propose alternative nomenclature to facilitate research on this unique patient population. Additionally, evidence supporting the various therapies used in the treatment of myositis-associated ILD is reviewed. The classification and treatment of patients with myositis-associated ILD remains challenging. A standardized therapeutic approach to these patients is lacking, and prospective studies in the field are needed to determine optimal treatment regimens. [ABSTRACT FROM AUTHOR]

Lung function decline varies significantly in patients with lymphangioleiomyomatosis (LAM), impeding individualized clinical decision-making. Can we aid individualized decision-making in LAM by developing a dynamic prediction model that can estimate the probability of clinically relevant FEV 1 decline in patients with LAM before treatment initiation? Patients observed in the US National Heart, Lung, and Blood Institute (NHLBI) Lymphangioleiomyomatosis Registry were included. Using routinely available variables such as age at diagnosis, menopausal status, and baseline lung function (FEV 1 and diffusing capacity of the lungs for carbon monoxide [D lco ]), we used novel stochastic modeling and evaluated predictive probabilities for clinically relevant drops in FEV 1. We formed predictive probabilities of transplant-free survival by jointly modeling longitudinal FEV 1 and lung transplantation or death events. External validation used the UK Lymphangioleiomyomatosis Natural History cohort. Analysis of the NHLBI Lymphangioleiomyomatosis Registry and UK Lymphangioleiomyomatosis Natural History cohorts consisted of 216 and 185 individuals, respectively. We derived a joint model that accurately estimated the risk of future lung function decline and 5-year probabilities of transplant-free survival in patients with LAM not taking sirolimus (area under the receiver operating characteristic curve [AUC], approximately 0.80). The prediction model provided estimates of forecasted FEV 1 , rate of FEV 1 decline, and probabilities for risk of prolonged drops in FEV 1 for untreated patients with LAM with a high degree of accuracy (AUC > 0.80) for the derivation cohort as well as the validation cohort. Our tool is freely accessible at: https://anushkapalipana.shinyapps.io/testapp%5fv2/. Longitudinal modeling of routine clinical data can allow individualized LAM prognostication and assist in decision-making regarding the timing of treatment initiation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate physiological phenotypes of asthma in obesity. Do physiological responses during bronchoconstriction distinguish different groups of asthma in people with obesity, and also differentiate from responses simply related to obesity? Cross-sectional study of people with obesity (31 with asthma and 22 without lung disease). Participants underwent methacholine challenge testing with measurement of spirometry and respiratory system impedance by oscillometry. Participants had class III obesity (BMI, 46.7 ± 6.6 kg/m2 in control subjects and 47.2 ± 8.2 kg/m2 in people with asthma). Most participants had significant changes in peripheral airway impedance in response to methacholine: in control subjects, resistance at 5 Hz measured by oscillometry increased by 45% ± 27% and area under the reactance curve (AX) by 268% ± 236% in response to 16 mg/mL methacholine; in people with asthma, resistance at 5 Hz measured by oscillometry increased by 52% ± 38% and AX by 361% ± 295% in response to provocation concentration producing a 20% fall in FEV 1 dose of methacholine. These responses suggest that obesity predisposes to peripheral airway reactivity. Two distinct groups of asthma emerged based on respiratory system impedance: one with lower reactance (baseline AX, 11.8; interquartile range, 9.9-23.4 cm H 2 O/L) and more concordant bronchoconstriction in central and peripheral airways; the other with high reactance (baseline AX, 46.7; interquartile range, 23.2-53.7 cm H 2 O/L) and discordant bronchoconstriction responses in central and peripheral airways. The high reactance asthma group included only women, and reported significantly more gastroesophageal reflux disease, worse chest tightness, more wheeze, and more asthma exacerbations than the low reactance group. Peripheral airway reactivity detected by oscillometry is common in obese control subjects and obese people with asthma. There is a subgroup of obese asthma characterized by significant peripheral airway dysfunction by oscillometry out of proportion to spirometric airway dysfunction. This peripheral dysfunction represents clinically significant respiratory disease not readily assessed by spirometry. [ABSTRACT FROM AUTHOR]

Background: The burden of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing worldwide. Amidst the poor treatment success of antibiotic therapy, adjunctive surgery is gaining attention; however, discrepancies in reported outcomes exist.Research Question: What are the treatment outcomes and complications of patients with NTM-PD undergoing adjunctive surgery?Study Design and Methods: The MEDLINE, Embase, and Cochrane databases were searched for eligible studies before January 2022. Studies reporting the outcomes of adjunctive surgery in adult patients who satisfied the diagnostic criteria for NTM-PD were included. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Data were extracted by two independent observers. Estimates of proportion were pooled using a random-effects model. Sputum mycobacterial culture negative conversion, recurrence, complications, and in-hospital mortality after surgery were primary outcomes that had been set before data collection began. Heterogeneity was evaluated by using the I2 statistic, and publication bias was assessed by using funnel plots and the Egger test.Results: Fifteen of the 2,739 screened studies, with 1,071 patients, were assessed. The weighted proportion of postoperative sputum culture negative conversion was 93% (95% CI, 87%-97%), and recurrence was 9% (95% CI, 6%-14%) for a median follow-up of 34 months. The proportion of patients who experienced postoperative complications was 17% (95% CI, 13%-23%), and in-hospital mortality was 0% (95% CI, 0%-2%). Studies that performed multilobar lung resection in > 30% of the study population showed comparable rates of complications with studies that did not.Interpretation: Adjunctive surgery is an effective therapeutic option with acceptable rates of complications for selected patients with NTM-PD.Trial Registry: PROSPERO; No.: CRD42022310663; URL: https://www.crd.york.ac.uk/prospero/. [ABSTRACT FROM AUTHOR]

Slowly growing nontuberculous mycobacteria (NTM) comprise a diverse group of environmental organisms, many of which are important human pathogens. The most common and well-known member of this group is Mycobacterium avium , the leading cause of nontuberculous mycobacterial pulmonary disease (NTM-PD) globally. This review focuses on the less common, but notable, species of slowly growing NTM with respect to lung disease. To prepare this article, literature searches were performed using each species name as the key word. Society guidelines were consulted, and relevant articles also were identified through the reference lists of key articles. The specific organisms highlighted include Mycobacterium kansasii , Mycobacterium xenopi , Mycobacterium malmoense , Mycobacterium simiae, and Mycobacterium szulgai. Although these organisms are closely related, they have distinct epidemiologic features and behavior as pathogens. Therefore, the diagnosis and management of NTM-PD require a nuanced approach that takes into consideration the unique characteristics of each species. There is limited evidence to inform the optimal treatment of NTM-PD. Antimicrobial therapy is often challenging because of the presence of drug resistance and few antibiotic options. Regimen selection should generally be guided by drug susceptibility testing, although the correlation between clinical outcomes and in vitro susceptibility thresholds has not been defined for most species. [ABSTRACT FROM AUTHOR]

There is now ample evidence that differences in sex and gender contribute to the incidence, susceptibility, presentation, diagnosis, and clinical course of many lung diseases. Some conditions are more prevalent in women, such as pulmonary arterial hypertension and sarcoidosis. Some life stages-such as pregnancy-are unique to women and can affect the onset and course of lung disease. Clinical presentation may differ as well, such as the higher number of exacerbations experienced by women with cystic fibrosis (CF), more fatigue in women with sarcoidosis, and more difficulty in achieving smoking cessation. Outcomes such as mortality may be different as well, as indicated by the higher mortality in women with CF. In addition, response to therapy and medication safety may also differ by sex, and yet, pharmacogenomic factors are often not adequately addressed in clinical trials. Various aspects of lung/sleep biology and pathobiology are impacted by female sex and female reproductive transitions. Differential gene expression or organ development can be impacted by these biological differences. Understanding these differences is the first step in moving toward precision medicine for all patients. This article is the second part of a state-of-the-art review of specific effects of sex and gender focused on epidemiology, disease presentation, risk factors, and management of selected lung diseases. We review the more recent literature and focus on guidelines incorporating sex and gender differences in pulmonary hypertension, CF and non-CF bronchiectasis, sarcoidosis, restless legs syndrome and insomnia, and critical illness. We also provide a summary of the effects of pregnancy on lung diseases and discuss the impact of sex and gender on tobacco use and treatment of nicotine use disorder. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) is a common comorbidity of nontuberculous mycobacteria (NTM) pulmonary disease (PD). Although GERD is associated with more symptoms and severe disease in patients with NTM PD, whether GERD is associated with an increased risk of NTM PD developing is unknown. Does GERD influence the development of NTM PD? Are there any factors associated with an increased risk of NTM PD among patients with GERD? What is the impact of NTM PD on the health-care use of patients with GERD? Data from the Korean National Health Insurance Service National Sample Cohort between 2002 and 2015 were used. The incidence and risk of NTM PD were compared between patients with GERD (GERD cohort; n = 17,424) and patients matched for age, sex, type of insurance, and Charlson Comorbidity Index (matched cohort; n = 69,696). Using the GERD cohort, the factors associated with incident NTM PD also were evaluated. During a median follow-up duration of 5.1 years, the age- and sex-adjusted incidence of NTM PD was significantly higher in the GERD cohort (34.8 per 100,000 person-years [PY]) than in the matched cohort (10.5 per 100,000 PY; P <.001), with a subdistribution hazard ratio (HR) of 3.36 (95% CI, 2.10-5.37). Regarding risk factors associated with NTM PD, age of 60 years or older (adjusted HR, 3.57; 95% CI, 1.58-8.07) and bronchiectasis (adjusted HR, 18.69; 95% CI, 6.68-52.28) were associated with an increased risk of incident NTM PD in the GERD cohort. Compared with patients with GERD who did not demonstrate NTM PD, those with NTM PD showed higher all-cause (13,321 PY vs 5,932 PY; P =.049) and respiratory disease-related (5,403 vs 801; P =. 011) ED visits or hospitalizations. GERD is associated with an increased incidence of NTM PD. Older age and bronchiectasis are risk factors for NTM PD in patients with GERD. NTM PD in patients with GERD is associated with increased health-care use. [Display omitted] [ABSTRACT FROM AUTHOR]

A 17-month-old male infant with history of an abnormal chest shadow in the left lung lower lobe was admitted to our hospital for the resection of the malformation. At 9 months of age, he was admitted to his local hospital because of a persistent cough. The chest CT scan in his local hospital indicated a cystic lesion in the left lung lower lobe associated with inflammation. However, no thoracic abnormalities were seen in antenatal ultrasonography, and no clinical symptoms were observed at birth. After anti-inflammatory treatments given to this infant, he achieved remission and was discharged from his local hospital. [ABSTRACT FROM AUTHOR]

A 59-year-old woman sought treatment for 5 weeks of progressive exercise intolerance. At the time of presentation, dyspnea limited her ability to speak in complete sentences. She also reported new orthopnea. Her respiratory symptoms improved with rest and while standing. She endorsed associated intermittent low-grade fevers, cough productive of scant clear sputum, lower extremity swelling, bloating, weight loss, and reduced appetite. She had undergone two recent admissions with similar symptoms to other hospitals, during which she was treated empirically for community-acquired pneumonia and discharged after workups for infectious disease were unrevealing. She had a history notable for systemic lupus erythematosus (SLE) diagnosed in 2006, complicated by lupus nephritis in 2009. Most recently, her SLE had been quiescent while she was taking hydroxychloroquine (400 mg daily) and mycophenolate mofetil (MMF; 1 g twice daily). She reported baseline mild dyspnea with exertion since she received a diagnosis of SLE, but her symptoms had not previously affected her activities of daily living. The patient did not smoke, drink alcohol, or use recreational drugs, and her family history was unremarkable. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is a chronic GI inflammatory disorder involving various extraintestinal organs, including the lungs. Although UC-related lung diseases (UC-LDs) have been widely recognized, much remains unclear.Research Question: What are the incidence, characteristics, clinical course, and risk factors of UC-LD?Study Design and Methods: This study retrospectively identified and classified UC-LDs by reviewing the medical records of consecutive patients with UC. The incidence, characteristics, and clinical course of each UC-LD type were investigated, and the clinical characteristics of patients with and without each UC-LD type were compared.Results: Among 563 patients with UC, 28 (5.0%) developed UC-LD during a mean follow-up period of 77 months. A majority of them displayed airway disease (AD) (n = 13 [2.3%]) or organizing pneumonia (OP) (n = 10 [1.8%]); there were six cases of interstitial pneumonias other than OP (IP) (0.8%) and one of pleuritis (0.2%). All 13 patients with AD responded favorably to inhaled or systemic corticosteroids, although five experienced frequent exacerbations. Older age and a history of colectomy were identified as the risk factors for developing AD. Nine of the 10 cases of OP were possibly due to drug-induced pathogenesis. Only one case showed recurrence, and all cases of OP exhibited a favorable clinical course with discontinuation of the suspicious drug and/or initiation of corticosteroid. The clinical course of IP depended on the existence of fibrosis, and IP with fibrosis was associated with gradual deterioration. Older age was associated with the development of IP.Interpretation: A nonnegligible number of patients with UC may develop UC-LD. AD, OP, and IP without fibrosis show good prognosis following steroid therapy along with the specific management for each UC-LD type, whereas IP with fibrosis shows gradual deterioration with poor prognosis. Our results provide cues to establish better management of UC-LDs. [ABSTRACT FROM AUTHOR]

Background: Prognostic prediction of nontuberculous mycobacteria pulmonary disease using a deep learning technique has not been attempted.Research Question: Can a deep learning (DL) model using chest radiography predict the prognosis of nontuberculous mycobacteria pulmonary disease?Study Design and Methods: Patients who received a diagnosis of nontuberculous mycobacteria pulmonary disease at Seoul National University Hospital (training and validation dataset) between January 2000 and December 2015 and at Seoul Metropolitan Government-Boramae Medical Center (test dataset) between January 2006 and December 2015 were included. We trained DL models to predict the 3-, 5-, and 10-year overall mortality using baseline chest radiographs at diagnosis. We tested the predictability for the corresponding mortality using only DL-driven radiographic scores and using both radiographic scores and clinical information (age, sex, BMI, and mycobacterial species).Results: The datasets comprised 1,638 (training and validation set) and 566 (test set) chest radiographs from 1,034 and 200 patients, respectively. The Dl-driven radiographic score provided areas under the receiver operating characteristic curve (AUC) of 0.844, 0.781, and 0.792 for 10-, 5-, and 3-year mortality, respectively. The logistic regression model using both the radiographic score and clinical information provided AUCs of 0.922, 0.942, and 0.865 for the 10-, 5, and 3-year mortality, respectively.Interpretation: The DL model we developed could predict the mid-term to-long-term mortality of patients with nontuberculous mycobacteria pulmonary disease using a baseline radiograph at diagnosis, and the predictability increased with clinical information. [ABSTRACT FROM AUTHOR]

The terms sex and gender often are used interchangeably, but have specific meaning when it comes to their effects on lung disease. Ample evidence is now available that sex and gender affect the incidence, susceptibility, presentation, diagnosis, and severity of many lung diseases. Some conditions are more prevalent in women, such as asthma. Other conditions are seen almost exclusively in women, like lymphangioleiomyomatosis. Some life stages-such as pregnancy-are unique to women and can affect the onset and course of lung disease. Clinical presentation may differ as well, such as higher number of exacerbations experienced by women with COPD and greater cardiovascular morbidity in women with sleep-disordered breathing. In addition, response to therapy and medication safety may also differ by sex, and yet, pharmacogenomic factors often are not addressed adequately in clinical trials. Various aspects of lung and sleep biology and pathobiology are impacted by female sex and female reproductive transitions. Differential gene expression or organ development can be impacted by these biological differences. Understanding these differences is the first step in moving toward precision medicine for women. This article is a state-of-the-art review of specific effects of sex and gender focused on epidemiology, disease presentation, risk factors, and management of lung diseases. Pathobiological mechanisms explaining sex differences in these diseases are beyond the scope of this article. We review the literature and focus on recent guidelines about using sex and gender in research. We also review sex and gender differences in lung diseases. [ABSTRACT FROM AUTHOR]

Background: Previous studies showed that the lung clearance index (LCI) determined by multiple-breath washout (MBW) is sensitive to detecting early lung disease in preschool children with cystic fibrosis (CF). In preschool children with primary ciliary dyskinesia (PCD), data on the onset and severity of lung disease and on the sensitivity of the LCI as a noninvasive quantitative outcome measure remain limited.Research and Study Question: Is MBW feasible and sensitive to detect ventilation inhomogeneity in preschool children with PCD?Study Design and Methods: This was a prospective, cross-sectional, multicenter study and included preschoolers with PCD, preschoolers with CF, and healthy control (HC) participants. LCI was determined using nitrogen MBW and was compared among the three groups.Results: LCI was determined in 27 children with PCD, 34 children with CF, and 30 HC participants (mean age, 4.8 years; range, 2.2-6.9 years). The LCI in preschool children with PCD was increased (median, 9.1; 95% CI, 8.6-10.3) compared with HC participants (median, 7.0; 95% CI, 6.7-7.1; P < .0001), but did not differ from preschool children with CF (median, 8.6; 95% CI, 8.4-9.7; P = .71). The feasibility in the PCD group was 93.1% and was similar to that in the CF group (91.9%) and in HC participants (85.7%; P = .55).Interpretation: This study demonstrated early onset of lung disease in preschool children with PCD and indicated that lung disease severity in PCD may be similar to that in CF during preschool years. These data support a need for early diagnostic monitoring and therapy and suggest the LCI as a noninvasive diagnostic tool and as a potential end point in clinical trials testing early interventions in children with PCD. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2-related ARDS is associated with endothelial dysfunction and profound dysregulation of the thrombotic-fibrinolytic pathway. Defibrotide is a polyanionic compound with fibrinolytic, antithrombotic, and antiinflammatory properties.Research Question: What is the safety and tolerability of defibrotide in patients with severe SARS-CoV-2 infections?Study Design and Methods: We report a prospective, open-label, single-center safety trial of defibrotide for the management of SARS-CoV-2-related ARDS. Eligible participants were 18 years of age or older with clinical and radiographic signs of ARDS, no signs of active bleeding, a serum D-dimer of more than twice upper limit of normal, and positive polymerase chain reaction-based results for SARS-CoV-2. Defibrotide (6.25 mg/kg/dose IV q6h) was administered for a planned 7-day course, with serum D-dimer levels and respiratory function monitored daily during therapy.Results: Twelve patients (median age, 63 years) were treated, with 10 patients receiving mechanical ventilation and 6 receiving vasopressor support at study entry. The median D-dimer was 3.25 μg/ml (range, 1.33-12.3) at study entry. The median duration of therapy was 7 days. No hemorrhagic or thrombotic complications occurred during therapy. No other adverse events attributable to defibrotide were noted. Four patients met the day 7 pulmonary response parameter, all four showing a decrease in serum D-dimer levels within the initial 72 h of defibrotide therapy. Three patients died of progressive pulmonary disease 11, 17, and 34 days after study entry. Nine patients (75%) remain alive 64 to 174 days after initiation of defibrotide. Day 30 all-cause mortality was 17% (95% CI, 0%-35%). All patients with a baseline Pao2 to Fio2 ratio of ≥ 125 mm Hg survived, whereas the three patients with a baseline Pao2 to Fio2 ratio of < 125 mm Hg died.Interpretation: The use of defibrotide for management of SARS-CoV-2-related ARDS proved safe and tolerable. No hemorrhagic or thrombotic complications were reported during therapy, with promising outcomes in a patient population with a historically high mortality rate.Trial Registry: ClinicalTrials.gov; No.: NCT04530604; URL: www.Clinicaltrials: gov. [ABSTRACT FROM AUTHOR]

Background: Lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH) are cystic lung diseases in which a neoplastic cell is thought to be responsible for disease pathogenesis. The neoplastic LAM cell has mutations in the TSC genes, TSC1 or TSC2, whereas the neoplastic PLCH cell may have mutations in several genes (eg, BRAF, NRAS, MAP2K1). These mutations are not specific for PLCH and have been described in multiple cancers. TSC1 or TSC2 mutations and loss of heterozygosity (LOH) have also been described in cancers.Research Question: Is TSC2 LOH specific to LAM or is it also found in PLCH?Study Design and Methods: We recruited patients with LAM (n = 53) and healthy volunteers (n = 22) and compared the presence of cells with TSC2 LOH with patients with PLCH (n = 12). Blood and urine samples were collected for analysis. Fluorescence-activated cell sorting (FACS) was used to identify subpopulations of cells from blood and urine samples. We isolated CD45-CD235a-, CD45-CD235a+, and CD45+CD235a- cells from blood after density gradient separation. Cells were screened for TSC2 LOH at five microsatellites markers (ie, kg8, D16S3395, D16S3024, D16S521, D16S291). We obtained four cell subpopulations from urine (ie, CD44v6+CD9+, CD44v6+CD9-, CD44v6-CD9+, CD44v6-CD9-).Results: Using FACS, cells were isolated from blood and urine from patients with PLCH that showed TSC2 LOH. Healthy volunteers did not have cells with TSC2 LOH. As a control, cells isolated from blood and urine from patients with LAM gave results similar to those reported previously. These data show that TSC2 LOH is found in patients with cystic lung diseases with potential neoplastic characteristics, and in patients with cancer.Interpretation: The presence of TSC2 LOH in circulating cells is not specific for LAM. The data suggest that chromosomal abnormalities affecting the TSC2 gene are found in other diseases associated with cells having cancer-like neoplastic cells. [ABSTRACT FROM AUTHOR]