Background: Limited data exist on the reliability, efficacy and safety of ultrasound-guided transbronchial cryobiopsy for suspicious mediastinal and hilar lesions. This study shares findings from implementing this method and compares the results with those of the standard endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Methods: Patients undergoing diagnostic bronchoscopy for mediastinal or hilar lesions in four Swiss centres were included. The study aims to assess the diagnostic yield and safety of EBUS-guided cryobiopsy compared with EBUS-TBNA. Tunnelling to the target lesion was performed using an electric needle knife (70.8%), a 19 G- (12.4%) or a 22 G needle (16.8%). Cryobiopsies were obtained with a freezing time of 4–7 s (18.2% with a 1.7 mm probe) or 6–10 s (81.8% with a 1.1 mm probe). Results: Altogether, 137 patients were enrolled with a median follow-up of 89 days. The overall diagnostic yield was 56.2% for EBUS-TBNA and 91.2% for cryobiopsies (p<0.001). Cryobiopsies increased the diagnostic yield for benign disorders (+28.5%), uncommon tumours (+5.9%) and other metastatic cancer (+0.6%), but not for lung cancer (+0%). For lung cancer (n=27), immunohistochemistry was obtainable in 40.7% of EBUS-TBNA (median of 3 probes [IQR 3 to 3]), significantly lower than cryobiopsy’s 88.9% yield (median of 4 probes [IQR 3 to 5]) (p<0.001). Adverse events were found in 23.4% of participants; 10.2% had mild to moderate bleeding, 0.7% had pneumonia, and 0.7% (one) of patients had pneumothorax following pneumomediastinum. No deaths or mediastinum infections were observed. Conclusion: Cryobiopsy of mediastinal and hilar lesions improves the diagnostic yield compared with EBUS-TBNA while maintaining a favourable safety profile.

Patients with sarcoidosis experience fatigue and excessive daytime sleepiness (EDS). However, the underlying pathomechanism is unclear. Studies suggested undiagnosed obstructive sleep apnea (OSA) to be an important contributor, but reliable data on prevalence and impact of OSA in sarcoidosis are scarce. 71 adult patients with sarcoidosis, 1-to-1 matched to 71 adult controls according to sex, age, and body mass index were included. Participants underwent structured interviews (including Epworth Sleepiness Scale [ESS], Fatigue Assessment Scale [FAS], and Functional Outcome of Sleep Questionnaire [FOSQ-30]) and level-3 respiratory polygraphy. OSA was defined as apnea-hypopnea index ≥ 5 events/h. Prevalence of OSA was assessed and possible risk factors for OSA in sarcoidosis were investigated. Mild OSA (AHI ≥ 5 events/h) was prevalent in 32 (45%) sarcoidosis patients vs 22 (31%) controls (P = .040). Sarcoidosis patients presented higher ESS compared with matched controls (P = .037). FAS scores (median [quartile] of 21.5 [16, 27.5]) indicated fatigue in sarcoidosis patients. Patients with EDS (ESS ≥ 11) presented reduced FOSQ-30 results (median [quartile] of 16.7 [15.2, 17.8]). ESS, FAS, and FOSQ were not associated with AHI in sarcoidosis patients. Body mass index, sex, neck circumference, and NoSAS score were predictors for OSA in sarcoidosis. The risk for mild OSA is 2.5-fold higher in sarcoidosis patients compared with matched controls. OSA seems not to be the reason for increased sleepiness or fatigue in sarcoidosis. Risk factors such as body mass index, sex, neck circumference, and NoSAS score can be used to screen for OSA in sarcoidosis patients. Registry: ClinicalTrials.gov; Name: Obstructive Sleep Apnoea in Sarcoidosis (OSASA); URL: https://clinicaltrials.gov/ct2/history/NCT04156789?V_2=View; Identifier: NCT04156789. Roeder M, Sievi NA, Schneider A, et al. The prevalence of obstructive sleep apnea in sarcoidosis and its impact on sleepiness, fatigue, and sleep-associated quality of life: a cross-sectional study with matched controls (the OSASA study). J Clin Sleep Med. 2022;18(10):2415-2422.

Achieving adequate immunosuppression for lung transplant recipients in the first year after lung transplantation is a key challenge. Prophylaxis of allograft rejection must be balanced with the adverse events associated with immunosuppressive drugs, for example infection, renal failure, and diabetes. A triple immunosuppressive combination is standard, including a steroid, a calcineurin inhibitor, and an antiproliferative compound beginning with the highest levels of immunosuppression and a subsequent tapering of the dose, usually guided by therapeutic drug monitoring and considering clinical results, bronchoscopy sampling results, and additional biomarkers such as serum viral replication or donor-specific antibodies. Balancing the net immunosuppression level required to prevent rejection without overly increasing the risk of infection and other complications during the tapering phase is not well standardized and requires repeated assessments for dose-adjustments. In our adaptive immunosuppression approach, we additionally consider results from the white blood cell counts, in particular lymphocytes and eosinophils, as biomarkers for monitoring the level of immunosuppression and additionally use them as therapeutic targets to fine-tune the immunosuppressive strategy over time. The concept and its rationale are outlined, and areas of future research mentioned.

Transbronchial lung biopsy is routinely performed to identify acute cellular rejection (ACR) in lung transplant recipients (LTRs). This trial evaluates the clinical value of forceps and cryobiopsies versus cryobiopsies as a standalone diagnostic tool. In this randomized trial, LTRs were randomly assigned to receive either 2 cryobiopsies (cryobiopsy group) or a combination of 5 forceps- and 2 cryobiopsies (combined group). The primary outcome was the diagnostic yield to detect ACR; the secondary outcome was the incidence of ACR. We conducted a paired, intraindividual comparison in the combined group alongside interindividual comparisons. A total of 80 LTRs were randomly assigned to the cryobiopsy group (n = 40) or the combined group (n = 40) with 90 and 87 procedures performed, respectively. The diagnostic yield for ACR in the cryobiopsy group was similar to the combined group (95.6% vs 97.7%, p = 0.430). The sole use of cryobiopsies did not lead to a lower ACR incidence compared to the combined group (10% vs 17.2%, risk ratio 2.21 [95% confidence interval (CI) 0.67-7.29]; p = 0.190). Adverse events did not differ between the 2 groups (60.9% vs 57.5%, p = 0.655). The pneumothorax rate was overall 1.7%. There were no deaths or occurrences of severe bleeding. Cryobiopsies did not detect lower ACR than the combined group and can be used as primary and standalone diagnostic tools for histologic assessment of ACR without requiring forceps biopsies.

(1) Background: Mortality is a major outcome in research on chronic obstructive pulmonary disease (COPD) with various predictors described. However, the dynamic courses of important predictors over time are disregarded. This study evaluates if longitudinal assessment of predictors provides additional information on the mortality risk in COPD when compared with a cross-sectional analysis.; (2) In a longitudinal, prospective, non-interventional cohort study including mild to very severe COPD patients, mortality and its various possible predictors were annually assessed up to seven years.; (3) Results: 297 patients were analysed. Mean (SD) age was 62.5 (7.6) years and 66% males. Mean (SD) FEV1 was 48.8 (21.4)%. A total of 105 events (35.4%) happened with a median (95% CI) survival time of 8.2 (7.2/NA) years. No evidence for a difference between the raw variable and the variable history on the predictive value for all tested variables over each visit was found. There was no evidence for changing effect estimates (coefficients) across the study visits due to the longitudinal assessment; (4) Conclusions: We found no evidence that predictors of mortality in COPD are time dependent. This implies that cross-sectional measured predictors show robust effect estimates over time and multiple assessments seem not to change the predictive value of the measure.