Introduction: Lung cancer is the second most common cancer; however, synchronous lung cancer is rare and challenging to treat. Case Presentation: We report the case of an 80-year-old female patient who presented with two lung lesions with primary tumor characteristics, which revealed squamous cell carcinoma and synchronous adenocarcinoma after histological sampling. Next-generation sequencing (NGS) analysis revealed a MET Exon 14 skipping mutation in squamous cell carcinoma and an epidermal growth factor receptor mutation in adenocarcinoma. Capmatinib and stereotactic radiotherapy were initiated for the adenocarcinoma with a good clinical response. Capmatinib treatment had to be discontinued because of stage 3 edema of the lower limbs, after which a left lobectomy was performed. Currently, the patient is considered to be in remission. Conclusion: This case highlights the need for histological analysis of every lung lesion with primary tumor characteristics, as well as for NGS analysis in search of specific mutations enabling the introduction of targeted therapies. mesenchymal-epithelial transition.

BACKGROUND:Good data quality is essential when rare disease registries are used as a data source for pharmacovigilance studies. This study investigated data quality of the Swiss cystic fibrosis (CF) registry in the frame of a European Cystic Fibrosis Society Patient Registry (ECFSPR) project aiming to implement measures to increase data reliability for registry-based research. METHODS:All 20 pediatric and adult Swiss CF centers participated in a data quality audit between 2018 and 2020, and in a re-audit in 2022. Accuracy, consistency and completeness of variables and definitions were evaluated, and missing source data and informed consents (ICs) were assessed. RESULTS:The first audit included 601 out of 997 Swiss people with CF (60.3 %). Data quality, as defined by data correctness ≥95 %, was high for most of the variables. Inconsistencies of specific variables were observed because of an incorrect application of the variable definition. The proportion of missing data was low with <5 % for almost all variables. A considerable number of missing source data occurred for CFTR variants. Availability of ICs varied largely between centers (10 centers had >5 % of missing documents). After providing feedback to the centers, availability of genetic source data and ICs improved. CONCLUSIONS:Data audits demonstrated an overall good data quality in the Swiss CF registry. Specific measures such as support of the participating sites, training of data managers and centralized data collection should be implemented in rare disease registries to optimize data quality and provide robust data for registry-based scientific research.

Among the new therapeutic developments in pulmonology during 2021, we have identified three topics of interest. A new biotherapy is now available for the management of severe uncontrolled non-Th2 asthma. In the field of pulmonary arterial hypertension, upfront triple therapy at the time of diagnosis is associated with a survival benefit in high-risk patients. Riociguat is a therapeutic option for patients that remain at intermediate risk despite treatment with iPDE5. Sotatercept, a promising new class of drug for treatment of group 1 PAH will soon be available. Finally, the use of transbronchial cryobiopsies as a valid alternative to surgical lung biopsy for the diagnosis of diffuse interstitial lung diseases will also be discussed in this review.

The combination of elexacaftor, tezacaftor, ivacaftor (ETI) has revolutionised the care of individuals with cystic fibrosis, resulting in significant improvements in lung function and pulmonary exacerbations. Although the treatment is generally well tolerated, the impact of its discontinuation on lung function is not well documented. We report 3 cases of acute respiratory exacerbation and lung function decline occurring after ETI interruption. Common observed features of ETI interruption in these cases are: a) lung function decline (occurring within days to weeks), b) worsening of FEV 1 with a drop of more than 20% and to levels lower than pre-treatment, and c) clinical and functional improvement after resumption of ETI. This potential complication should be communicated to the patients prior to treatment initiation.

Ultrasound of the diaphragm is an emerging technique that is performed at the bedside and allows assessment of diaphragm function in a variety of settings. Ultrasound is widely available, can be repeated if necessary, and is non-irradiating. First developed in intensive care, mainly for weaning from mechanical ventilation, its use is now extending to pulmonology. Different measurements are described such as diaphragmatic excursion, diaphragmatic thickness and diaphragmatic thickening fraction. The latter helps to diagnose dysfunction and is correlated with pulmonary hyperinflation. The main use in pulmonology is for the respiratory evaluation of patients with neuromuscular diseases, for the search of isolated diaphragmatic impairment and for patients with COPD. Numerous studies are in progress to better determine the role of diaphragmatic ultrasound.

In this review of the recent medical literature, we have identified 4 topics of interest for the readers of Revue Médicale Suisse. Use of antifibrotic drugs in interstitial lung diseases will soon be extended to a phenotype labeled « progressive fibrosing interstitial lung disease » (PF-ILD). While awaiting for evidence-based treatment, consensual recommendations for a treatment algorithm in pulmonary sarcoidosis has been published. New guidance for non-invasive ventilation in COPD and obesity-hypoventilation syndrome are available in Switzerland and are in line with international recommendations. New treatments targeting CFTR protein activity have become available and could become a therapeutic option for up to 85% of cystic fibrosis patients in Switzerland.

Background: During the first wave of the SARS-CoV-2 pandemic in Switzerland, confinement was imposed to limit transmission and protect vulnerable persons. These measures may have had a negative impact on perceived quality of care and symptoms in patients with chronic disorders. Objectives: To determine whether patients under long-term home noninvasive ventilation (LTHNIV) for chronic respiratory failure (CRF) were negatively affected by the 56-day confinement (March–April 2020). Methods: A questionnaire-based survey exploring mood disturbances (HAD), symptom scores related to NIV (S3-NIV), and perception of health-care providers during confinement was sent to all patients under LTHNIV followed up by our center. Symptom scores and data obtained by ventilator software were compared between confinement and the 56 days prior to confinement. Results: Of a total of 100 eligible patients, 66 were included (median age: 66 years [IQR: 53–74]): 35 (53%) with restrictive lung disorders, 20 (30%) with OHS or SRBD, and 11 (17%) with COPD or overlap syndrome. Prevalence of anxiety (n = 7; 11%) and depressive (n = 2; 3%) disorders was remarkably low. Symptom scores were slightly higher during confinement although this difference was not clinically relevant. Technical data regarding ventilation, including compliance, did not change. Patients complained of isolation and lack of social contact. They felt supported by their relatives and caregivers but complained of the lack of regular contact and information by health-care professionals. Conclusions: Patients under LTHNIV for CRF showed a remarkable resilience during the SARS-CoV-2 confinement period. Comments provided may be helpful for managing similar future health-care crises.

Rationale and objectives Prone positioning as a complement to oxygen therapy to treat hypoxaemia in coronavirus disease 2019 (COVID-19) pneumonia in spontaneously breathing patients has been widely adopted, despite a lack of evidence for its benefit. We tested the hypothesis that a simple incentive to self-prone for a maximum of 12 h per day would decrease oxygen needs in patients admitted to the ward for COVID-19 pneumonia on low-flow oxygen therapy. Methods 27 patients with confirmed COVID-19 pneumonia admitted to Geneva University Hospitals were included in the study. 10 patients were randomised to self-prone positioning and 17 to usual care. Measurements and main results Oxygen needs assessed by oxygen flow on nasal cannula at inclusion were similar between groups. 24 h after starting the intervention, the median (interquartile range (IQR)) oxygen flow was 1.0 (0.1–2.9) L·min−1 in the prone position group and 2.0 (0.5–3.0) L·min−1 in the control group (p=0.507). Median (IQR) oxygen saturation/fraction of inspired oxygen ratio was 390 (300–432) in the prone position group and 336 (294–422) in the control group (p=0.633). One patient from the intervention group who did not self-prone was transferred to the high-dependency unit. Self-prone positioning was easy to implement. The intervention was well tolerated and only mild side-effects were reported. Conclusions Self-prone positioning in patients with COVID-19 pneumonia requiring low-flow oxygen therapy resulted in a clinically meaningful reduction of oxygen flow, but without reaching statistical significance.

Révolution dans le traitement de la mucoviscidose La mucoviscidose est une maladie génétique entraînant une absence ou des dysfonctions de la protéine Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), un canal chlore présent à la surface des épithélia, notamment respiratoire.Jusqu'à récemment, les traitements ne concernaient que les conséquences de la maladie.Mais un nouveau type de molécules appelées « modulateurs » est déjà à la disposition de certains patients et cible l'origine de la maladie.Les « modulateurs » sont divisés en « potentiateurs », permettant d'améliorer le transport du chlore par la protéine CFTR, et en « correcteurs », augmentant la quantité de protéines CFTR.Une trithérapie orale combinant un potentiateur et deux correcteurs vient d'être approuvée aux États-Unis et permettra de traiter 85 % des patients.Le bénéfice clinique des « modulateurs » est remarquable et ces médicaments bouleversent le traitement de la mucoviscidose. Revolution in the treatment of cystic fibrosisCystic Fibrosis is a genetic disorder resulting in the absence or dysfunction of the CFTR protein, a chloride channel present on the surface of epithelia, particularly respiratory.Until recently, treatments only concerned the consequences of the disease.But a new type of molecules called « modulators », is already available to some patients and targets the origin of the disease.« Modulators » are divided into « potentiators », which improve the transport of chloride by the CFTR protein, and « correctors », increasing the amount of CFTR proteins.An oral triple therapy combining a potentiator and two correctors has just been approved in the USA and will treat 85 % of patients.The clinical benefit of « modulators » is remarkable, and these drugs are revolutionizing the treatment of Cystic Fibrosis.

Cystic Fibrosis is a genetic disorder resulting in the absence or dysfunction of the CFTR protein, a chloride channel present on the surface of epithelia, particularly respiratory. Until recently, treatments only concerned the consequences of the disease. But a new type of molecules called « modulators », is already available to some patients and targets the origin of the disease. « Modulators » are divided into « potentiators », which improve the transport of chloride by the CFTR protein, and « correctors », increasing the amount of CFTR proteins. An oral triple therapy combining a potentiator and two correctors has just been approved in the USA and will treat 85 % of patients. The clinical benefit of « modulators » is remarkable, and these drugs are revolutionizing the treatment of Cystic Fibrosis.

Systemic lupus erythematosus is a multisystem autoimmune disease with wide-ranging pleuropulmonary manifestations. Acute lupus pneumonitis is one of its uncommon complications. We report a 36-year-old woman with acute lupus pneumonitis as the initial presentation of systemic lupus erythematosus. Clinical, biological, radiological and functional improvements were noticed with the administration of steroids, hydroxychloroquine and immunoglobulin.

Fibrinolysis can be used to improve fluid drainage in pleural infection. Treatment with either urokinase or tissue plasminogen activator (t-PA) in association with DNAse via a chest tube has been effective at reducing the need for surgery. This study is the first to compare the efficacy of these two treatments. We performed a single-centre, controlled, prospective cohort study. All individuals with pleural infection admitted to our hospital between January 2014 and December 2017 who were treated with antibiotics, a chest tube and fibrinolysis were included in this study. The rate of additional procedure requirements (additional chest tube or surgery) after initial fibrinolysis, complications, costs, and radiological and biological outcomes were analysed. Among the 93 patients included in this study, 34% required additional procedures after an initial fibrinolysis, including 21% who received an additional chest tube and 13% who underwent thoracoscopy. The need for additional procedures arose due to presence of multiple pleural collections (p=0.01) and was associated with the use of large-bore drain (p=0.01). The success rate of fibrinolysis was not significantly different between urokinase and t-PA/DNAse (p=0.35). The differences in drainage duration and in length of hospital stay were not significant either (p=0.05 and p=0.12, respectively). Treatment with t-PA/DNAse was cheaper (p=0.04) but was associated with a higher rate of haemothorax (p=0.002). In conclusion, treatment with urokinase is safer and equally effective when compared with treatment with t-PA/DNAse.

Introduction. We report on our clinical experience implementing stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer using deep inspiration breath-hold (DIBH) and real-time tumour tracking, via implanted electromagnetic transponders (EMT). Preliminary data for our first two patients are presented, SBRT lung treatments using real-time tracking with EMT are ongoing at our institution.

The group of non-tuberculous mycobacteria (NTM) – also referred to as environmental mycobacteria – includes more than 150 species of the genus Mycobacterium distinct from the Mycobacterium tuberculosis complex. A limited number of these intracellular acid-fast bacilli may be pathogenic for humans and cause a necrotizing granulomatous inflammation. The most frequent clinical manifestations of NTM are lung infections, adenitis, skin infections, and bacteremia in immunosuppressed hosts. Not all species are pathogenic in humans and the risk of developing a clinical disease depends on the equilibrium between the pathogenicity of the strain and host characteristics (e.g., immunosuppression, comorbidities).Over the last decades, there has been an increasing awareness of NTM infections in the medical community. Epidemiological data in the US, Europe, and other parts of the world show an increase in prevalence and incidence of NTM isolation [1]. The association between certain respiratory disorders and NTM is well known, but specific data regarding the clinical and prognostic impact of identifying NTM in COPD patients are scarce [2]. In COPD, NTM may be associated with a higher incidence of acute exacerbations and a more rapid deterioration of pulmonary function [3].The development of endoscopic lung volume reduction (ELVR) in severe COPD has led to invasive bacterial sampling in patients who would have been otherwise unlikely to undergo bronchoscopy. It is standard procedure in our center to perform systematic cultures for mycobacteria from bronchial aspirates collected during every bronchoscopy.We report a series of 44 patients with severe COPD who underwent ELVR between October 2013 and October 2017 at our hospital, from which we retrospectively collected bacteriological findings from all bronchial aspirates obtained during the procedure.All patients included met the eligibility criteria for ELVR, namely: emphysema, persisting dyspnea despite maximal medical therapy including recent rehabilitation, age <75 years, being an ex-smoker for >6 months, FEV1 <45% of predicted, marked hyperinflation (residual volume >175% of predicted), 6-min walking distance >140 m, and no or few acute exacerbations during the year prior to the procedure. In all patients, chest computed tomography (CT) showed severe emphysema. Only one patient, who previously underwent a single lung transplant a few years ago, was immunosuppressed.NTMs were isolated in 8/44 patients (18.2% of cases) (Table 1). Mycobacterium avium complex was the most prevalent NTM identified (5/8, all M. avium subtype). Other NTM identified were: Mycobacterium xenopi (n = 1), Mycobacterium gordonae (n = 1) and a rapidly growing NTM (n = 1; rapidly growing, non-pigmented).At the time of ELVR, none of the patients had images suggestive of NTM infection on CT scans. From 8 patients with NTM isolation, only 4 had an opacity or nodule on the CT. Interestingly, no patient with NTM isolation had bronchiectasis.None of the samples were microscopy positive. NTM were isolated once in most patients (6/8), twice in one, and three times in another. Of the 8 patients with NTM isolation, two had a single bronchoscopy, three had 2 bronchoscopies, two had 3 bronchoscopies, and one had 4. With a mean follow-up of 993 days (range: 420–1,566), no patient required specific antimycobacterial treatment for NTM-associated lung disease, according to ATS/ERS criteria [4].Other pathogens isolated from bronchial aspirates were Haemophilius influenzae (4/44 patients), various gram-negative bacilli (11/44 patients), and Aspergillus species (6/44 patients).The rate of NTM colonization in our cohort is significantly higher than previously reported in such a population. Moreover, this rate is significantly higher than the overall NTM identification rate we have in our global bronchoscopy population in our center, which is 6% (22 bronchial aspirates out of 358, p = 0.01, t test). This suggests that these patients are particularly susceptible to colonization when exposed and may therefore be at higher risk of developing active NTM infection. In this retrospective study, however, with an average follow-up period of approximately 3 years, no patient developed an active NTM disease.We found no difference between patients with or without NTM colonization in terms of severity of obstruction, use of steroids (oral or inhaled), or any other cause of immunosuppression. Given the retrospective design of this report and the small number of patients, we are unable to assess the clinical impact of NTM identification on lung function and disease progression. However, the frequent colonization by NTM in severe COPD suggests that NTM infection may be underestimated in this population. The clinical impact of this finding has to be further explored by larger prospective studies, but it seems reasonable to recommend a systematic search for NTM in COPD patients before initiating immunomodulatory macrolide treatments, in frequent exacerbators, and in presence of a rapid decline of FEV1.Geneva University Hospitals.Nothing to disclose.No external funding.

Background and purposes: Motion management is crucial for optimal stereotactic body radiotherapy (SBRT) of moving targets. We aimed to describe our clinical experience with real-time tracking of lung-specific electromagnetic transponders (EMTs) for SBRT of early stage non-small cell lung cancer in free-breathing (FB) or deep inspiration breath-hold (DIBH). Material and methods: Seven patients were implanted with EMTs. Simulation for SBRT was performed in FB and in DIBH. We prescribed 60 Gy in 3, 5 or 8 fractions to the tumor and delivered SBRT with volumetric modulated arcs and a 6 MV flattening filter free photon beam. Patients' setup at the linac was performed using EMT positions and cone-beam CT (CBCT) verification. Four patients were treated in DIBH because of a dosimetric benefit. We analysed patient alignment and treatment delivery parameters using DIBH or FB and EMT real-time tracking. Results: There were no complications from the EMT implantation. Visual inspection of CBCT before and/or after SBRT revealed good alignment of structures and EMTs. The median setup time was 9.8 min (range: 4.6-34.1 min) and the median session time was 14.7 min (range: 7.3-36.5 min). EMT positions in lungs remained stable during overall treatment and allowed real-time tracking both in FB and in DIBH SBRT. The treatment beam was gated when EMT centroid position exceeded tolerance thresholds ensuring correct delivery of radiation to the tumor. Conclusion: Using EMTs for real-time tracking of tumor motion during lung SBRT proved to be safe, accurate and easy to integrate clinically for treatments in FB or DIBH.