American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · May 2024
Multicenter StudyHigher Molecular Injury at Diagnosis of Acute Cellular Rejection Increases the Risk of Lung Allograft Failure.
Rationale: The association of acute cellular rejection (ACR) with chronic lung allograft dysfunction (CLAD) in lung transplant recipients has primarily been described before consensus recommendations incorporating restrictive phenotypes. Furthermore, the association of the degree of molecular allograft injury during ACR with CLAD or death remains undefined. Objectives: To investigate the association of ACR with the risk of CLAD or death and to further investigate if this risk depends on the degree of molecular allograft injury. ⋯ Patients with high-risk ACR were at increased risk of CLAD or death (HR, 3.13; 95% CI, 1.41-6.93; P = 0.005), whereas patients with low-risk status ACR were not. Conclusions: Patients with ACR are at higher risk of CLAD or death, but this may depend on the degree of underlying allograft injury at the molecular level. Clinical trial registered with www.clinicaltrials.gov (NCT02423070).
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Am. J. Respir. Crit. Care Med. · May 2024
A Novel Air Trapping Segment Score Identifies Opposing Effects of Obesity and Eosinophilia on Air Trapping in Asthma.
Rationale: Density thresholds in computed tomography (CT) lung scans quantify air trapping (AT) at the whole-lung level but are not informative for AT in specific bronchopulmonary segments. Objectives: To apply a segment-based measure of AT in asthma to investigate the clinical determinants of AT in asthma. Methods: In each of 19 bronchopulmonary segments in CT lung scans from 199 patients with asthma, AT was categorized as present if lung attenuation was less than -856 Hounsfield units at expiration in ⩾15% of the lung area. ⋯ The AT segment score in patients with sputum eosinophils ⩾2% was higher than in patients without sputum eosinophilia (7.0 ± 6.1 vs. 3.3 ± 4.9; P < 0.0001). Lung segments with AT more frequently had airway mucus plugging than lung segments without AT (48% vs. 18%; P ⩽ 0.0001). Conclusions: In patients with asthma, air trapping is more severe in those with airway eosinophilia and mucus plugging, whereas those who are obese have less severe trapping because their lower lobe segments are spared.
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Am. J. Respir. Crit. Care Med. · May 2024
Serum Cell-free DNA-based Detection of Mycobacterium Avium Complex Infection.
Rationale: Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial (NTM) pulmonary disease (PD), which exhibits increasing global incidence. Current microbiologic methods routinely used in clinical practice lack sensitivity and have long latencies, leading to delays in diagnosis and treatment initiation and evaluation. A clustered regularly interspaced short palindromic repeats (CRISPR)-based assay that measures MAC cell-free DNA (cfDNA) concentrations in serum could provide a rapid means to detect MAC infection and monitor response to antimicrobial treatment. ⋯ Measurements and Main Results: The CRISPR MAC assay detected MAC cfDNA in MAC PD with 97.6% (91.6-99.7%) sensitivity and 97.6% (91.5-99.7%) specificity overall. Serum MAC cfDNA concentrations markedly decreased after MAC-directed treatment initiation in patients with MAC PD who demonstrated MAC culture conversion. Conclusions: This study provides preliminary evidence for the utility of a serum-based CRISPR MAC assay to rapidly detect MAC infection and monitor the response to treatment.