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Background: Fraction of exhaled nitric oxide with an expiratory flow of 50 mL/s (FENO50) is a biomarker of eosinophilic airway inflammation. Liver transplant recipients have an increased risk of pulmonary infections, but little is known about the burden of chronic pulmonary diseases in this group. We aimed to assess the prevalence of elevated FENO50 in liver transplant recipients and compare it to controls from the general population. Methods: FENO50 was measured in 271 liver transplant recipients from The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study and 1,018 age- and sex-matched controls from The Copenhagen General Population Study (CGPS). Elevated FENO50 was defined as ≥25 or ≥50 parts per billion (ppb). The analyses were adjusted for known and suspected confounders. Results: The median age of the liver transplant recipients was 55 years (interquartile range (IQR) 46-64), and 58% were men. The liver transplant recipients had a higher median FENO50 than the controls [16 ppb (IQR 10-26) vs. 13 ppb (IQR 8-18.), p < 0.001]. Furthermore, the liver transplant recipients had a higher prevalence of elevated FENO50 (for FENO50 ≥25 ppb 27% vs. 11%, p < 0.001 and ≥50 ppb 4% vs. 2%, p = 0.02). The results were similar after adjusting for age, sex, smoking status, use of airway medication, and blood eosinophil counts [the adjusted odds ratio (OR) for FENO50 ≥25 ppb was 3.58 (95% CI: 2.50-5.15, p < 0.0001) and the adjusted OR for FENO50 ≥50 ppb was 3.14 (95% CI: 1.37-7.20, p = 0.007)]. Conclusion: The liver transplant recipients had elevated FENO50, implying increased eosinophilic airway inflammation. The clinical impact of this finding needs further investigation.
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Transplante de Fígado , Óxido Nítrico , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Estudos de Coortes , Transplante de Fígado/efeitos adversos , Eosinófilos , InflamaçãoRESUMO
Transbronchial lung cryobiopsy (TBLC) is an invasive procedure increasingly implemented during the last decade as an alternative to video-assisted thoracic surgery lung biopsy (SLB) for diagnosing interstitial lung diseases (ILDs). The indication for TBLC has primarily been to sub-classify a specific ILD subtype when this cannot be achieved on the basis of a preceding multidisciplinary team discussion. Although SLB is considered the gold standard for establishing a histological diagnosis, TBLC has been gradually suggested as the first-choice histological diagnostic modality in patients with unclassified ILDs due to a comparable diagnostic yield with SLB, but superior to SLB in terms of complications, including mortality. During recent years, radial endobronchial ultrasound (R-EBUS) and electromagnetic navigation bronchoscopy (ENB)-guided TBLC for peripheral pulmonary lesions have also been described as safe procedures, which may improve the diagnostic yield compared to forceps biopsies. Still, the diagnostic properties of TBLC rely on the quality of the procedure's performance. This article aims to describe the stepwise approach to conducting TBLC with a flexible bronchoscope for the different indications mentioned, which might be helpful for novice bronchoscopists performing TBLC.
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Doenças Pulmonares Intersticiais , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Biópsia , Broncoscopia , Endossonografia , Pulmão/diagnóstico por imagemRESUMO
Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants, genome-wide, may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ⩽0.01) within genes or regions. We also identified individual rare variants that are influential within genes and estimated the heritability of IPF on the basis of rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP heritability of IPF was estimated to be 32% (SE = 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or the development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.
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Fibrose Pulmonar Idiopática , Humanos , Fibrose Pulmonar Idiopática/genética , Sequenciamento Completo do Genoma , ExomaRESUMO
BACKGROUND: Chronic pulmonary aspergillosis (CPA) can complicate underlying pulmonary diseases, and clinical management of CPA is challenging. Guidelines support clinicians but due to the complexity of the disease they can be difficult to adhere to. OBJECTIVES: To map current guideline recommendations for the clinical management of CPA into a scoring tool to facilitate and quantify guideline adherence in clinical practice. METHODS: Recommendations for diagnosis, treatment and follow-up of CPA presented in the current ESCMID/ERS/ECMM and CPAnet guidance documents were assembled and weighed on the basis of their strength of recommendation and level of evidence. RESULTS: Twenty-seven recommendations were identified, resulting in a total maximum EQUAL CPA Score of 51. For diagnostics (ScoreMaxâ=â27), a strong emphasis on expert consultation, culture, direct microscopy, histopathology, serology and imaging was reflected in respective points, whereas molecular techniques and susceptibility testing count into the diagnostics score to a lesser extent.Ten treatment recommendations (ScoreMaxâ=â14), including antifungal therapy, therapeutic drug monitoring and treatment duration, were identified. Surgery, where indicated, adds three points. For refractory disease or intolerance of first-line antifungal treatment, optimal second-line treatment added another two points.During follow-up (ScoreMaxâ=â10), response assessment via imaging gave three points, while culture and serology added two points each to the ScoreMax. CONCLUSION: The EQUAL CPA Score intents to be used as a comprehensive tool for measuring guideline adherence. If adherence to current guidelines is associated with clinical outcome, this will be assessed in future studies.
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Antifúngicos , Aspergilose Pulmonar , Humanos , Antifúngicos/uso terapêutico , Fidelidade a Diretrizes , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/tratamento farmacológico , Tomografia Computadorizada por Raios X , Doença CrônicaRESUMO
The first ever research prioritisation exercise in GLILD: this survey identified areas of interest in the diagnosis, treatment and management of GLILD, which can be used as a roadmap for future research https://bit.ly/3nVuzti.
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BACKGROUND: The aim of the study was to determine the diagnostic yield and prevalence of complications of ultrasound-guided transthoracic needle aspiration biopsies (US-TTNAB) performed by respiratory physicians after implementation of the procedure in an everyday clinical setting at 3 different centers. METHODS: Patients were included if they during the period from January 2012 to August 2014 had a registered US-TTNAB procedure code or if a US biopsy registration form had been filled out at either of the participating centers. Histology or cytology results were used as a reference test for diagnoses that could be made based on these results. Reference test for the remaining diagnoses was clinical follow-up. The diagnostic yield of US-TTNAB was defined as the proportion of patients in which the result of the US-TTNAB was consistent with the reference test. RESULTS: A total of 215 patients in which a primary US-TTNAB had been performed were identified. The most common biopsy sites were lungs and pleurae with a total of 164 (76.3%) patients and 31 patients (14.4%), respectively. US-TTNAB diagnostic yield was 76.9% (95% CI, 70.3%-83.4%) for malignant diagnoses and 47.6% (95% CI, 31.9%-63.4%) for nonmalignant diagnoses. The most common complications of US-TTNAB were pneumothorax (2.5%; 95% CI, 0.03%-4.6%) and pain at the biopsy site (2%; 95% CI, 0.04%-3.9%). No fatalities related to US-TTNAB were observed. CONCLUSION: US-TTNAB performed by respiratory physicians is a safe procedure with a low risk of complications and the diagnostic yield to establish a malignant diagnosis is acceptable.