The effect of longitudinal sleep monitoring on clinician agreement in obstructive sleep apnea diagnosis: The ELSA study.

There is strong evidence for clinically relevant night-to-night variability of respiratory events in patients with suspected obstructive sleep apnea. Sleep experts retrospectively evaluated diagnostic data in 56 patients with suspected obstructive sleep apnea. Experts were blinded to the fact that they were diagnosing the same case twice, once based on a short report of a single in-laboratory respiratory polygraphy and once with the additional information of 14 nights of pulse oximetry at home. All experts (n = 22) were highly qualified, 13 experts (59.1%) treated > 100 patients with suspected obstructive sleep apnea per year. In 12 patients, the apnea-hypopnea index in the respiratory polygraphy was < 5 per hr, but the mean oxygen desaturation index of 14 nights of pulse oximetry was ≥ 5 per hr. The additional information of 14 nights of pulse oximetry helped to diagnose obstructive sleep apnea with a 70% consensus in two of those patients (16.7% [95% confidence interval: 4.7/44.8]). In eight patients, experts could not agree to a 70% consensus regarding continuous positive airway pressure therapy recommendation after respiratory polygraphy. The additional information of multiple-night testing led to a consensus in three of those cases (37.5% [95% confidence interval: 14/69]). Change of obstructive sleep apnea diagnosis and continuous positive airway pressure recommendation was significantly negatively associated with the number of treated obstructive sleep apnea patients > 100 per year compared with 0-29 patients per year (Coef. [95% confidence interval] -0.63 [-1.22/-0.04] and -0.61 [-1.07/-0.15], respectively). Experts found already a high level of consensus regarding obstructive sleep apnea diagnosis, severity and continuous positive airway pressure recommendation after a single respiratory polygraphy. However, longitudinal sleep monitoring could help increase consensus in selected patients with diagnostic uncertainty.

One-Lung Ventilation during Rigid Bronchoscopy Using a Single-Lumen Endotracheal Tube: A Descriptive, Retrospective Single-Center Study.

Using one-lung ventilation (OLV) through a single-lumen endotracheal tube (SLT) in the untreated lung during rigid bronchoscopy (RB) and jet ventilation, high oxygenation can be guaranteed, whilst procedures requiring thermal energy in the other lung are still able to be used. This pilot study aimed to examine the bronchoscopy-associated risks and feasibility of OLV using an SLT during RB in patients with malignant airway stenosis. All consecutive adult patients with endobronchial malignant lesions receiving OLV during RB from 1 January 2017 to 12 May 2021 were included. We assessed perioperative complications in 25 RBs requiring OLV. Bleeding grades 1, 2, and 3 complicated the procedure in two (8%), five (20%), and five (20%) patients, respectively. The median saturation of peripheral oxygen remained at 94% (p = 0.09), whilst the median oxygen supply did not increase significantly from 0 L/min to 2 L/min (p = 0.10) within three days after the bronchoscopy. The 30-day survival rate of the patients was 79.1% (95% CI 58.4-91.1%), all of whom reported an improvement in subjective well-being after the bronchoscopy. OLV using an SLT during RB could be a new treatment approach for endobronchial ablative procedures without increasing bronchoscopy-associated risks, allowing concurrent high-energy treatments.

Lung Ultrasound for the Exclusion of Pneumothorax after Interventional Bronchoscopies-A Retrospective Study.

A chest X-ray (CXR) is recommended after bronchoscopies with an increased risk of pneumothorax (PTX). However, concerns regarding radiation exposure, expenses and staff requirements exist. A lung ultrasound (LUS) is a promising alternative for the detection of PTX, though data are scarce. This study aims to investigate the diagnostic yield of LUS compared to CXR, to exclude PTX after bronchoscopies with increased risk. This retrospective single-centre study included transbronchial forceps biopsies, transbronchial lung cryobiopsies and endobronchial valve treatments. Post-interventional PTX screening consisted of immediate LUS and CXR within two hours. In total, 271 patients were included. Early PTX incidence was 3.3%. Sensitivity, specificity, and the positive and negative predictive values of LUS were 67.7% (95% CI 29.93-92.51%), 99.2% (95% CI 97.27-99.91%), 75.0% (95% CI 41.16-92.79%) and 98.9% (95% CI 97.18-99.54%), respectively. PTX detection by LUS enabled the immediate placement of two pleural drains along with the bronchoscopy. With CXR, three false-positives and one false-negative were observed; the latter evolved into a tension-PTX. LUS correctly diagnosed these cases. Despite low sensitivity, LUS enables early diagnosis of PTX, thus preventing treatment delays. We recommend immediate LUS, in addition to LUS or CXR after two to four hours and monitoring for signs and symptoms. Prospective studies with higher sample sizes are needed.

Improved glucose tolerance after initiation of Elexacaftor / Tezacaftor / Ivacaftor in adults with cystic fibrosis.

BACKGROUND: The novel triple CFTR modulator therapy Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) improves lung function, body mass index (BMI), sinus clearance, and quality of life in patients with cystic fibrosis. Whether treatment with ELX/TEZ/IVA is associated with improved glucose tolerance is unknown. METHODS: This cohort study included adults with CF and at least one copy of F508del.. Study assessments before treatment and at least 3 months after ELX/TEZ/IVA initiation included an oral glucose tolerance test (OGTT) with glucose and insulin measurements, BMI, lung function test, and sweat chloride levels. We used an analysis of response profiles to calculate changes in outcomes. RESULTS: 33 patients (27.8 ± 6.3 years; 73% male; 64% F508del homozygous) were included. After a median of 184 [IQR, 107 - 278] days following treatment initiation 16 (48.5%) patients improved their glucose tolerance category, while 13 (39.4%) remained unchanged and 4 (12.1%) deteriorated. Overall, 60, 90 and 120 min OGTT glycemia decreased significantly from 11.9 ± 2.7 mmol/l to 10.6 ± 2.8 mmol/l (p = 0.012), 10.4 ± 3.0 mmol/l to 8.4 ± 3.6 mmol/l (p = 0.002) and 7.3 ± 3.1 mmol/l to 5.7 ± 3.0 mmol/l (p = 0.012). HbA1c levels also improved significantly, from 5.50±0.24% to 5.39±0.25% (p = 0.039). CONCLUSION: In adult patients with CF and at least one copy of F508del, treatment with the triple CFTR modulator was associated with possible improvement of glucose tolerance without increases of insulin secretion. Early initiation of treatment as assessed through long-term prospective trials is mandatory to demonstrate if decreased glucose control is preventable or even reversible.

Cost-effectiveness analysis of surgical lung volume reduction compared with endobronchial valve treatment in patients with severe emphysema.

BACKGROUND: Lung volume reduction, either by surgery or bronchoscopically by endobronchial valve treatment have been shown to be a cost-effective alternative compared with conservative therapy. However, there is no comparative analysis of lung volume reduction by surgery and bronchoscopic lung volume reduction using endobronchial valves. OBJECTIVES: The aim of this retrospective study was to provide a cost-effectiveness analysis of lung volume reduction by surgery compared with bronchoscopic lung volume reduction using endobronchial valves. METHODS: The effectiveness of lung volume reduction was assessed using forced expiratory volume in the first second (FEV1), residual volume (RV) and 6-minute walking distance (6MWD), measured at baseline and at 4 to 12 weeks. Cost unit accounting derived from SwissDRG was used as a surrogate of the costs from the payer's perspective. RESULTS: In total, 67 patients (37 men and 30 women) with a mean age of 68.3 ± 7.4 years were included. Both clinical effectiveness and costs were comparable between surgical and bronchoscopic lung reduction. The incremental cost-effectiveness ratios (ICERs) for bronchoscopic compared with lung volume reduction by surgery for FEV1, RV and 6MWD were -101, 4 and 58, respectively. For RV and 6MWD, it could be shown that endobronchial valve treatment is justified as a probably cost-effective alternative to lung volume reduction by surgery. Endobronchial valve treatment resulted in an improvement of 0.25 quality-adjusted life years (QALYs) and an ICER of € 7657 per QALY gained. CONCLUSION: A robust statement on the superiority of one of the two procedures in terms of cost-effectiveness cannot be made from the present study. Therefore, the study is not suitable for resource allocation. Two upcoming trials comparing lung volume reduction surgery and endobronchial valve treatment may be able to answer this question.

Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation.

BACKGROUND: Survival predictors are not established for cystic fibrosis (CF) patients listed for lung transplantation (LT). Using the deficit accumulation approach, we developed a CF-specific frailty index (FI) to allow risk stratification for adverse waitlist and post-LT outcomes. METHODS: We studied adult CF patients listed for LT in the Toronto LT Program (development cohort 2005-2015) and the Swiss LT centres (validation cohort 2008-2017). Comorbidities, treatment, laboratory results and social support at listing were utilized to develop a lung disease severity index (LI deficits, d = 18), a frailty index (FI, d = 66) and a lifestyle/social vulnerability index (LSVI, d = 10). We evaluated associations of the indices with worsening waitlist status, hospital and ICU length of stay, survival and graft failure. RESULTS: We studied 188 (Toronto cohort, 176 [94%] transplanted) and 94 (Swiss cohort, 89 [95%] transplanted) patients. The median waitlist times were 69 and 284 days, respectively. The median follow-up post-transplant was 5.3 and 4.7 years. At listing, 44.7% of patients were frail (FI ≥ 0.25) in the Toronto and 21.3% in the Swiss cohort. The FI was significantly associated with all studied outcomes in the Toronto cohort (FI and post-LT mortality, multivariable HR 1.74 [95%CI:1.24-2.45] per 0.1 point of the FI). In the Swiss cohort, the FI was associated with worsening waitlist status, post-LT mortality and graft failure. CONCLUSIONS: In CF patients listed for LT, FI risk stratification was significantly associated with waitlist and post-LT outcomes. Studying frailty in young populations with advanced disease can provide insights on how frailty and deficit accumulation impacts survival.

Influence of mycophenolate mofetil dosage and plasma levels on the occurrence of chronic lung allograft dysfunction in lung transplants: a retrospective cohort analysis.

INTRODUCTION: Development of chronic lung allograft dysfunction is a limiting factor for post-lung transplant survival. We evaluated whether the dose of the immunosuppressant mycophenolate mofetil or plasma concentrations of the active metabolite mycophenolic acid affect the development of chronic lung allograft dysfunction. METHODS: In this retrospective cohort study we recruited 71 patients with a lung transplant between 2010 and 2014 which survived the first year after transplantation up to 1 July 2021. An event-time-analytical Cox proportional-hazards regression model with time-varying-covariates (18,431 measurements for MPA, mycophenolate mofetil dosage, lymphocytes) was used to predict chronic lung allograft dysfunction, with adjustment for sociodemographic factors and lung function at baseline. RESULTS: 37 patients did not develop chronic lung allograft dysfunction (age 41.3 ± 15.6 years, baseline FEV1 95.5 ± 19.1% predicted) and 34 patients developed chronic lung allograft dysfunction (age 50.9 ± 13.3 years, baseline FEV1 102.2 ± 25.4% predicted). Mean mycophenolic acid did not differ significantly between the groups (2.8 ± 1.7 and 3.0 ± 2.3 mg/l; p = 0.724). In the first 4 post-transplant years the death rate was 25%. A total of 50% of the patients died by the ninth post-transplant year. There was a dose-effect relationship between mycophenolate mofetil dosage, mycophenolic acid (r2 = 0.02, p <0.001), as well as lymphocyte levels (r2 = -0.007, p <0.001), but only the traditional risk factor age predicted chronic lung allograft dysfunction. Continuously measured mycophenolic acid did not predict chronic lung allograft dysfunction (hazard ratio 0.98, 95% confidence interval 0.90-1.06, p = 0.64 over a period of 382.97 patient-years). CONCLUSION: Mycophenolate mofetil dosage and mycophenolic acid were not associated with chronic lung allograft dysfunction development. Thus, the mycophenolate mofetil dose or mycophenolic acid plasma concentration are not a primary factor related to organ rejection, but chronic lung allograft dysfunction may be influenced by other components of immunosuppression or other factors.

Endobronchial Ultrasound-Guided Transbronchial Forceps Biopsy: A Retrospective Bicentric Study Using the Olympus 1.5 mm Mini-Forceps.

When evaluating mediastinal/hilar lymphadenopathy (LAD) or masses, guidelines recommend endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) as an initial technique for tissue analysis and diagnosis. However, owing to the small sample size obtained by needle aspiration, its diagnostic yield (DY) is limited. EBUS transbronchial forceps biopsy (TBFB) used as a complimentary technique to EBUS-TBNA might allow for better histopathological evaluation, thus improving DY. In this retrospective bicentric study, we assessed the DY and safety of an EBUS-guided 1.5 mm mini-forceps biopsy combined with EBUS-TBNA for the diagnosis of mediastinal/hilar LAD or masses compared to EBUS-TBNA alone. In total, 105 patients were enrolled. The overall DY was 61.9% and 85.7% for TBNA alone and EBUS-TBNA combined with EBUS-TBFB, respectively (p < 0.001). While the combined approach was associated with a significantly higher DY for lung cancer diagnosis (97.1% vs. 76.5%, p = 0.016) and sarcoidosis (85.2% vs. 44.4%, p = 0.001), no significant differences in DY were calculated for subgroups with smaller sample sizes such as lymphoma. No major adverse events were observed. Using a 1.5 mm mini-forceps is a safe and feasible technique for biopsy of mediastinal or hilar LAD or masses with superior overall DY compared to EBUS-TBNA as a standalone technique.

Transbronchial Cryobiopsy Compared to Forceps Biopsy for Diagnosis of Acute Cellular Rejection in Lung Transplants: Analysis of 63 Consecutive Procedures.

BACKGROUND: Acute cellular rejection (ACR) is a complication after lung transplantation (LTx). The diagnosis of ACR is based on histologic findings using transbronchial forceps biopsy (FB). However, its diagnostic accuracy is limited because of the small biopsy size and crush artifacts. Transbronchial cryobiopsy (CB) provides a larger tissue size compared with FB. METHODS: FB and CB were obtained consecutively during the same bronchoscopy (February 2020-April 2021). All biopsies were scored according to the ISHLT criteria by three pathologists. Interobserver agreement was scored by the kappa index. We assessed the severity of bleeding and the presence of pneumothorax. RESULTS: In total, 35 lung transplant recipients were included, and 126 CBs and 315 FBs were performed in 63 consecutive bronchoscopies. ACR (A1-A3, minimal-moderate) was detected in 18 cases (28.6%) by CB, whereas ACR was detected in 3 cases (4.8%) by FB. Moderate and severe bleeding complicated FB and CB procedures in 23 cases (36.5%) and 1 case (1.6%), respectively. Pneumothorax occurred in 6.3% of patients. The interobserver agreement was comparable for both CB and FB. CONCLUSIONS: CB provided an improved diagnostic yield for ACR diagnosis, leading to reclassification and changes in treatment strategies in 28.6% of cases. Prospective studies should better define the role of CB after LTx.

Early Spirometry Following Bronchoscopic Lung Volume Reduction with Endobronchial Valves.

Bronchoscopic lung volume reduction (BLVR) by endobronchial valve (EBV) implantation has been shown to improve dyspnea, pulmonary function, exercise capacity, and quality of life in highly selected patients with severe emphysema and hyperinflation. The most frequent adverse event is a pneumothorax (PTX), occurring in approximately one-fifth of the cases due to intrathoracic volume shifts. The majority of these incidents are observed within 48 h post-procedure. However, the delayed occurrence of PTX after hospital discharge is a matter of concern. There is currently no approved concept for its prevention. Particularly, it is unknown whether and when respiratory manoeuvers such as spirometry post EBV treatment are feasible and safe. As per standard operating procedure at the University Hospital Zurich, early spirometry is scheduled after BLVR and prior to the discharge of the patient in order to monitor treatment success. The aim of our retrospective study was to investigate the feasibility and safety of early spirometry. In addition, we hypothesized that early spirometry could be useful to identify patients at risk for late PTX, which may occur after hospital discharge. All patients who underwent BLVR using EBVs between January 2018 and January 2020 at our hospital were enrolled in this study. After excluding 16 patients diagnosed post-procedure with PTX and four patients for other reasons, early spirometry was performed in 61 cases. There was neither a clinically relevant PTX during or after early spirometry nor a late PTX following hospital discharge. In conclusion, we found early spirometry, conducted not sooner than three days following EBV treatment, to be feasible and safe. Furthermore, early spirometry seems to be a useful predictor for successful BLVR, and it may help to decide whether a patient can be discharged. Given the small sample size and the retrospective design of our study, a prospective study that includes routine chest imaging after early spirometry to definitively exclude PTX is needed to recommend early spirometry as part of the standard protocol following EBV treatment.

Combined Pulmonary Fibrosis and Emphysema (CPFE) Clinical Features and Management.

BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) is an underrecognized syndrome characterized by chronic, progressive disease with a dismal prognosis. Frequent co-morbidities with a higher incidence than in idiopathic pulmonary fibrosis or emphysema alone are pulmonary hypertension (WHO group 3) in 47-90% of the patients and lung cancer in 46.8% of the patients. OBJECTIVE: Review current evidence and knowledge concerning diagnosis, risk factors, disease evolution and treatment options of CPFE. METHODS: We searched studies reporting CPFE in original papers, observational studies, case reports, and meta-analyses published between 1990 and August 2020, in the PubMed, Embase, Cochrane Library, Wiley Online Library databases and Google Scholar using the search terms [CPFE], [pulmonary fibrosis] OR [IPF] AND [emphysema]. Bibliographies of retrieved articles were searched as well. Further inclusion criteria were publications in English, French, German and Italian, with reference to humans. In vitro data and animal data were not considered unless they were mentioned in studies reporting predominantly human data. RESULTS: Between May 1, 1990, and September 1, 2020, we found 16 studies on CPFE from the online sources and bibliographies. A total of 890 patients are described in the literature. Although male/female ratio was not reported in all studies, the large majority of patients were male (at least 78%), most of them were current or former heavy smokers. CONCLUSION: CPFE is a syndrome presenting with dyspnea on exertion followed by disruptive cough and recurrent exacerbations. The disease may progress rapidly, be aggravated by pulmonary hypertension WHO group 3 and is associated with an increased risk of lung cancer. Smoking and male sex are important risk factors. There is a need for more research on CPFE especially relating to etiology, influence of genetics, treatment and prevention options. Antifibrotic therapy might be an interesting treatment option for these patients.

ECP as additional immunomodulation in idiopathic hyperammonemia and recurrent hypercapnic respiratory failure early post lung transplantation.

Extra-corporeal photopheresis (ECP) is known as safe ultimate treatment option for chronic lung allograft dysfunction (CLAD). Here, we report the first case of ECP as "second-line" immunomodulatory therapy early post-transplant in an adult patient undergoing lung transplantation for severe chronic thromboembolic pulmonary hypertension, complicated by impaired consciousness due to idiopathic hyperammonemia resulting in recurrent hypercapnic respiratory failure. ECP was initiated twice weekly on post-transplant day 25 and standard triple immunosuppression reduced. Within 2 weeks, the clinical status improved. ECP has been continued every 4 weeks after discharge. At 1 year post-transplant, ECP was stopped as maintenance immunosuppression was reached. We recommend to consider the immunomodulatory effect of ECP as "second line" immunomodulatory therapy in cases where standard immunosuppression causes severe collateral damage. ECP is able to assist prevention of allograft rejection in conjunction with reduced levels of standard immunosuppression, even in the early period following lung transplantation.

Calcineurin inhibitors revisited: A new paradigm for COVID-19?

Abstract The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can cause mild, moderate or severe disease (COVID-19). In severe disease, there is hyperinflammation causing severe symptoms. Severe COVID-19 is an immunological phenomenon, rather than a direct viral damage disease. Therapies for COVID-19 are all investigational therapies. In case of severe disease, treatment with a calcineurin inhibitor could be promising. In this article we explain the mechanisms of calcineurin inhibitor treatment for COVID-19, based on experiences seen in solid organ transplant recipients who suffered from COVID-19.

Calcineurin inhibitors revisited: A new paradigm for COVID-19?

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can cause mild, moderate or severe disease (COVID-19). In severe disease, there is hyperinflammation causing severe symptoms. Severe COVID-19 is an immunological phenomenon, rather than a direct viral damage disease. Therapies for COVID-19 are all investigational therapies. In case of severe disease, treatment with a calcineurin inhibitor could be promising. In this article we explain the mechanisms of calcineurin inhibitor treatment for COVID-19, based on experiences seen in solid organ transplant recipients who suffered from COVID-19.

Bronchoscopic thermal vapor ablation after unsuccessful lung volume reduction surgery: A case report.

Compared to surgery there is no evidence on bronchoscopic lung volume reduction (LVR) in patients with fading benefit after LVR surgery. CASE REPORT: We present a case of 64-year old female patient who was successfully treated with bronchial thermal vapor ablation (BTVA) after previous ineffective lung volume reduction (LVR) surgery several months earlier. CONCLUSIONS: Bronchoscopic LVR, in particular BTVA, might be considered in patients with fading or missing effects after previous LVRS. At least, the safety profile of BTVA seems not be adversely affected by previous LVRS, when proper patient selection and procedure planning are ensured.

The use of life-saving extracorporeal membrane oxygenation (ECMO) for pregnant woman with status asthmaticus.

INTRODUCTION: Status asthmaticus can develop into a life-threatening disorder that requires mechanical ventilation. Severe respiratory failure during pregnancy can worsen maternal and fetal outcomes. Previous case studies have demonstrated extracorporeal membrane oxygenation (ECMO) as a life-saving measure for pregnant women with acute respiratory distress syndrome (ARDS) as well as non-pregnant patients with status asthmaticus. CASE STUDY: A 25-year-old woman, who was 5 weeks pregnant, was admitted with status asthmaticus and severe hypercapnic respiratory failure. Despite rescue therapies such as pressure control ventilation with high inspiratory pressures, inhaled beta2 agonists and antimuscarinic drugs, intravenous salbutamol, methylprednisolone and magnesium sulfate, her condition gradually deteriorated. Veno-venous ECMO was initiated for respiratory support and the patient's clinical condition as well as the gas exchange improved within the next few days. ECMO was removed and the patient was extubated after 2 days. Sonography, however, revealed a retrochorial hematoma; the patient was diagnosed with abortus imminens and successfully treated with magnesium substitution and bed rest. Finally, she gave birth to a healthy boy at 38 weeks of gestation. CONCLUSIONS: This is the first case report on the successful use of ECMO in a pregnant woman with severe respiratory insufficiency due to status asthmaticus, who failed to respond to invasive mechanical ventilation and maximum pharmacological treatment. Despite this life-threatening condition, the use of ECMO in our patient has greatly improved the chance of survival for the mother and the baby, who was born without any complications.