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Background: Obstructive sleep apnea (OSA) causes episodes of fragmented sleep and intermittent hypoxia and leads to excessive daytime sleepiness (EDS). Deficits in cognitive function are a troublesome symptom in patients with OSA and EDS.

Research question: How does solriamfetol affect cognitive function in patients with cognitive impairment associated with OSA and EDS?

Study design and methods: SHARP was a phase 4, randomized, double-blind, placebo-controlled, crossover trial. Participants (N=59) were randomized to receive placebo or solriamfetol (75 mg/day for 3 days, then 150 mg/day) for 2 weeks, with crossover separated by a 1-week washout. Efficacy measures included the Coding subtest, comparable to the Digit Symbol Substitution Test, of the Repeatable Battery for the Assessment of Neuropsychological Status (DSST RBANS), the British Columbia Cognitive Complaints Inventory (BC-CCI), Patient Global Impression of Severity (PGI-S), and Epworth Sleepiness Scale (ESS). The primary endpoint was change from baseline in average post-dose DSST RBANS scores. Secondary endpoints were changes from baseline in BC-CCI, PGI-S, ESS, and DSST RBANS scores at 2, 4, 6, and 8 hours post-dose. Safety was monitored by treatment-emergent adverse events (TEAEs).

Results: Solriamfetol significantly improved post-dose average DSST RBANS scores compared with placebo (P=0.009; effect size [Cohen's d] 0.37). When evaluated at each 2-hour timepoint, cognitive function was significantly improved at 2, 6, and 8 hours after dosing (all P<0.05). During solriamfetol treatment, there were significant improvements in BC-CCI (P=0.002; d=0.45), PGI-S (P=0.0mixed; d=0.29), and ESS (P=0.004; d=0.40) compared with placebo. The most common TEAEs were nausea (7%) and anxiety (3%).

Interpretation: SHARP demonstrated that solriamfetol can improve objective and subjective measures of cognitive function in patients with cognitive impairment associated with OSA and EDS.

Clinical trial registration: NCT04789174; EudraCT: 2020-004243-92.

Background: Quantitative chest computed tomography (CT) may be a useful predictor of outcome in rheumatoid arthritis-related interstitial lung disease (RA-ILD).

Research question: What is the utility of deep learning-based lung fibrosis quantitation on CT in assessing disease severity, predicting mortality and identifying progression in RA-ILD?

Study design and methods: CT scans on a primary cohort of 289 and a validation cohort of 50 individuals with RA-ILD were assessed quantitatively by using the data-driven texture analysis (DTA) method. We examined associations between quantitative scores for extent of lung fibrosis and pulmonary function and survival.

Results: DTA fibrosis score at baseline showed moderate negative correlation with forced vital capacity (FVC) percentage predicted (primary cohort rho=-0.55, validation cohort rho= -0.50, p<0.001 for both), and diffusing capacity for carbon monoxide (DLCO) percentage predicted (primary cohort rho=-0.67, validation cohort rho=-0.65, p<0.001 for both). Longitudinal change in DTA fibrosis score was associated with changes in FVC and DLCO in the primary cohort (rho=-0.46 and rho=-0.43, respectively, p<0.001 for both). Cox multivariable models adjusted for potentially influential variables showed that the baseline DTA fibrosis score was significantly associated with mortality risk (primary cohort hazard ratio [HR] 1.04, 95% confidence interval [1.03, 1.05], p<0.001; validation cohort HR 1.06, 95% confidence interval [1.01, 1.11], p=0.026). In the primary cohort increase in DTA fibrosis score on sequential scans was associated with increased risk of mortality (HR 1.04, 95% confidence interval [1.01, 1.06], p=0.003) independent of baseline DTA extent.

Interpretation: In two cohorts of patients with RA-ILD, quantitative assessment of lung fibrosis on CT was associated with worse lung function at baseline and risk of mortality. Increase in DTA-derived lung fibrosis score on sequential scans was associated with subsequent risk of mortality. Quantitative CT should be considered for use as a clinical and research outcome assessment tool in RA-ILD.

Background: There are limited FDA-approved medications and real-world data on sarcoidosis treatment in the U.S. and concordance of practice patterns with guideline recommendations have not been well characterized.

Research question: What are the practice patterns and factors associated with treatment for patients with sarcoidosis in the year following diagnosis?

Study design and methods: We conducted a retrospective analysis of patients with sarcoidosis from 2016 - 2022 using a multicenter, all-payer, claims database (TriNetX). We ascertained treatments with corticosteroids and/or non-steroidal immunosuppressive medications (methotrexate, mycophenolate, leflunomide, hydroxychloroquine, cyclophosphamide, infliximab, adalimumab, azathioprine, rituximab, and janus kinase inhibitors) within one year of diagnosis. We summarized treatment rates, sequence of prescribed medications by mean rank, and used multivariable logistic regression analyses to identify factors associated with treatment.

Results: Out of 13,330 patients with sarcoidosis meeting inclusion, 5,671 (42.5%) received treatment within a year of diagnosis. Of those treated, 60% received steroids alone, 13% received non-steroidal immunosuppressives alone, and 27% received both. Further, 25% of treated patients received a non-steroidal immunosuppressive as their first medication. Corticosteroids had the lowest mean rank order, indicating they were, on average, the first medication initiated. Among those with pulmonary or cutaneous involvement, the second medication initiated on average was hydroxychloroquine, while in those with cardiac or neurologic involvement it was adalimumab and mycophenolate, respectively. Factors associated with higher odds of treatment were Black race, organ involvement at baseline (pulmonary, cardiac, and neurologic), and comorbid diagnoses (fatigue, hypercalcemia, and ILD).

Interpretation: Within the first year of diagnosis, 43% of patients with sarcoidosis were started on treatment. Non-steroidal immunosuppressives were used in 40% of treated patients. While factors associated with treatment initiation aligned with guideline recommendations, practice patterns of treatment were variable, particularly in choice and sequence of non-steroidal immunosuppressive therapy, underscoring the need for future trials and comparative effectiveness studies.

Background: Sarcoidosis is an idiopathic multiorgan disease with variable clinical outcomes. Comprehensive analysis of sarcoidosis mortality in U.S. Veterans is lacking.

Research questions: What are the trends in all-cause mortality among U.S. Veterans with sarcoidosis, and how are these trends influenced by demographics, Black vs. White racial disparities, and geographic variability in relation to mortality?

Study design and methods: Using Veterans Health Administration (VHA) electronic health records (EHR), we conducted a population-based, retrospective cohort study of adjusted all-cause mortality 2004-2022 among Veterans diagnosed with sarcoidosis who received care through the VHA. Demographics, region of residence, service branch, tobacco use, and comorbidities were extracted from EHR. Annual trends in all-cause mortality and patient-level characteristics associated with mortality were examined with multivariable ungrouped Poisson regression. We visualized trends and analyzed state-by-state mortality using the marginal means procedure. In subgroup analysis (2015-2022), we considered the impact of neighborhood-level socioeconomic disparities using the area deprivation index (ADI).

Results: In all, 23,745 Veterans were diagnosed with sarcoidosis between 2004 and 2019 and followed through 2022. After adjustment, including age and sex, all-cause mortality increased annually by 4.7% (P<0.0001) and was 6.4% higher in Black than White Veterans (mortality rate ratio=1.064, P=0.02). A subgroup analysis comparing models with and without ADI adjustment showed no meaningful change in mortality trends. Risk factors for increased all-cause mortality included older age, male sex, Black race, and Northeast residence, and lower risk with "Other" service branches. Despite distinct geographical variations in mortality rates, no clear patterns emerged.

Interpretation: Mortality among Veterans with sarcoidosis is rising. Differences identified by service branch and higher risk among male Veterans raise questions about differences in environmental exposures. The narrower racial disparities and smaller impact of ADI than in other studies may highlight the role of universal healthcare access in achieving equitable outcomes.

Parasitic infections in the United States are mostly seen in immigrants and travelers. In many cases, pulmonary and intensive care physicians fail to consider parasitic disease, which can result in delayed diagnosis and adverse outcomes. Almost 2,000 cases of imported malaria are diagnosed in the United States each year. Severe cases can be confused with bacterial sepsis (shock, lactic acidosis, pneumonia, renal failure, respiratory failure, and jaundice). In contrast to bacterial sepsis, survival is improved by restrictive fluid therapy. Parenteral artesunate is licensed to treat severe cases but may not be readily accessible. Strongyloidiasis is endemic in warm and most tropical regions. Chronic strongyloidiasis causes few symptoms and can persist for decades after the patient leaves the endemic region. Treatment with corticosteroids may lead to hyperinfection, which may present with bacteremia and meningitis due to enteric organisms, pulmonary hemorrhage, and gastrointestinal pain, bleeding or obstruction. Treatment with ivermectin can be curative if initiated early. Cystic echinococcosis can present as pulmonary mass. Paragonimus presents with hemoptysis, pulmonary nodules, and/or pleural effusions, and usually with eosinophilia. Endemic regions include not only East Asia, but also Southeast Asia, west Africa, the Pacific coast of Latin America, and even North America. Other parasitic infections can involve the lungs. This article aims to provide awareness of the most clinically relevant parasitic infections seen in pulmonary and critical care medicine.

Background: Pneumothorax is a major complication following endoscopic lung volume reduction with valves with a prevalence of up to 34%. While some patients benefit from valve implantation despite pneumothorax, others are significantly impaired after lung collapse.

Research question: What are the differences in the severity grades of pneumothorax and how does that affect our clinical practice?

Study design and methods: This single-center retrospective study analyzed patients undergoing endoscopic valve implantation with and without post-interventional pneumothorax. Emphysema characteristics, collateral ventilation, management, and outcome of patients with pneumothorax 3 months after valve implantation were assessed. Pneumothorax was categorized as "severe pneumothorax" (chest tube insertion, prolonged air leak requiring valve removal), "moderate pneumothorax" (chest tube, no valve removal), and "mild pneumothorax" (no chest tube).

Results: Pneumothorax occurred in 102/532 patients (19%) and was significantly more common after valve placement in the upper lobes (31.3%) compared to the lower lobes (11.3%, p < 0.001). Fissure integrity was significantly higher in patients with pneumothorax (mean 96.6 ± 6.3 % vs. 93.4 ± 10.3 %, p = 0.002). Of all pneumothoraces, 30.4% were mild, 30.4% moderate, 39.2% severe. Severe pneumothorax caused multiple complications and prolonged hospitalization. Valve placement in the left upper lobe and a larger size of the target lobe were identified as risk factors for severe pneumothorax. Patients with pneumothorax developed complete lobar atelectasis in >60% as a sign of therapeutic success, but obviously only when valves could be left in place or re-implanted. However, valve re-implantation resulted in re-pneumothorax in 42.9%.

Interpretation: Patients could be more individually informed about their risk of pneumothorax, which varies with target lobe location, fissure integrity and re-implantation. The poor outcome and high complication rate of severe pneumothorax calls for future research into the prediction of severe pneumothorax.

Topic importance: Interstitial lung diseases (ILDs) represent a broad group of heterogeneous parenchymal lung diseases. Some ILDs progress, causing architectural distortion and pulmonary fibrosis, thus are called fibrotic ILDs. Recent studies have shown a beneficial effect of antifibrotic therapy in fibrotic ILDs other than Idiopathic Pulmonary Fibrosis (IPF) that manifest progressive pulmonary fibrosis (PPF). However, it is still challenging to predict which patients with fibrotic ILDs will manifest PPF. Precision medicine approaches could identify patients at risk for progression and guide treatment in patients with IPF or PPF.

Review findings: Multiple biomarkers able to highlight disease susceptibility risk, provide an accurate diagnosis, prognosticate or assess treatment response have been identified. Advances in precision medicine led to the identification of endotypes that could discriminate patients with different fibrotic ILDs or patients with different disease course. Importantly, recent studies have shown that particular compounds were efficacious only in particular endotypes. The aforementioned findings are promising. However, implementation in clinical practice is still an unmet need.

Summary: Substantial progress has been observed in the context of precision medicine approaches in fibrotic ILDs during the last years. Nonetheless, there are still infrastructure, financial, regulatory and ethical challenges to overcome for the implementation of precision medicine in the clinical practice. Overcoming such barriers and moving from ''one-size fits all'' approach to a patient-centered care could substantially improve patient's quality of life and survival.

Background: Guidelines advise minimising asthma exacerbation risk is achieved partially through good clinical practice activities, including scheduled asthma reviews, inhaler technique checks and asthma management plans. We assessed how frequently these activities are provided and how effective they are in clinical practice.

Research question: Do guidelines-recommended activities such as asthma reviews, inhaler technique checks and asthma management plans prevent asthma exacerbations STUDY DESIGN AND METHODS: This is a retrospective chart review using UK primary-care medical records between 2004-2021, linked to hospital records. Children were eligible from asthma diagnosis until aged 16 years. Annual implementation of asthma review, inhaler technique check, management plan was measured. Risk factors for them not being undertaken were determined using multivariable logistic regression. Self-controlled case series (SCCS) was adopted to assess the effectiveness of each activity over 12-months; this was divided into two 6-month periods.

Results: 126,483 children were eligible; 30-45% received each annual activity, 8% received all three together. Risk factors for not receiving activities included younger age, more socioeconomic deprivation, higher or no BMI measurement. Management plans and asthma reviews, as standalone activities, were associated with approximately 15% exacerbation reduction over 12-months and 8% over 6-months, respectively (management plan, N=4,624; 0-6 months (IRR, 95%CI): 0.87, 0.79-0.96; 6-12 months: 0.83, 0.73-0.95; asthma review, N=6,948; 0-6 months: 0.92, 0.85-0.99; 6-12 months: 0.93, 0.83-1.03). Standalone inhaler technique checks were not associated with exacerbations. Provision of all activities together was associated with approximately 30% exacerbation reduction over 12-months (N=3,643, 0-6 months: 0.76, 0.68-0.85; 6-12 months: 0.69, 0.60-0.81).

Interpretation: Most UK children do not receive the guideline-recommended activities to monitor their asthma. This study suggests, if implemented, they are effective in clinical practice and maximally effective when combined in the same visit.

Background: Patients with idiopathic pulmonary fibrosis (IPF) may suffer from insomnia and use hypnotics. However, the effect of the use of hypnotics on their clinical course remains unclear.

Research question: Is the use of hypnotics associated with an increased risk of mortality in patients with IPF?

Study design and participants: This study included 99 and 123 patients with IPF from the Hamamatsu and Seirei hospital-based cohorts, respectively, and 30,218 patients with IPF from the national claims database of Japan (NDB cohort). To analyze the association of hypnotic use with outcomes avoiding immortal time bias, multivariable Cox models with time-dependent covariates and target trial emulation with a new user design were employed for the hospital- and NDB-based cohorts, respectively.

Results: In the cohorts studied, the 3-year cumulative incidence of new use of hypnotics after IPF diagnosis was 13.4%-24.1%. In both the hospital-based cohorts, the continuous use of hypnotics was associated with an increased risk of all-cause mortality and disease progression. In the NDB cohort, the continuous use of hypnotics was also associated with an increased risk of all-cause mortality. Subgroup analysis found associations between the continuous use of hypnotics and increased mortality regardless of sex and comorbidities, excluding certain subpopulations.

Interpretation: This study found that continuous use of hypnotics was associated with an increased risk of mortality in patients with IPF. Given the relatively high cumulative incidence of hypnotic use in this population, there is an urgent need to reassess the appropriate use of hypnotics for patients with IPF.