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Barrier integrity is central to the maintenance of healthy immunological homeostasis. Impaired skin barrier function is linked with enhanced allergen sensitization and the development of diseases such as atopic dermatitis (AD), which can precede the development of other allergic disorders, for example, food allergies and asthma. Epidemiological evidence indicates that children suffering from allergies have lower levels of dietary fibre-derived short-chain fatty acids (SCFA). Using an experimental model of AD-like skin inflammation, we report that a fermentable fibre-rich diet alleviates systemic allergen sensitization and disease severity. The gut-skin axis underpins this phenomenon through SCFA production, particularly butyrate, which strengthens skin barrier function by altering mitochondrial metabolism of epidermal keratinocytes and the production of key structural components. Our results demonstrate that dietary fibre and SCFA improve epidermal barrier integrity, ultimately limiting early allergen sensitization and disease development.The Graphical Abstract was designed using Servier Medical Art images ( https://smart.servier.com ).

Immune checkpoint inhibitors (ICIs) have been shown to improve overall and progression-free survival in various cancers but have been associated with various immune-related adverse events (IRAEs), including interstitial lung disease, especially organizing pneumonia. We report 2 cases of isolated severe airway disease attributable to ICIs, a rarely reported pattern of lung toxicity. The first patient received nivolumab with or without ipilimumab in a randomized double-blind trial for locoregional metastatic melanoma. The second patient was treated with nivolumab for lung adenocarcinoma. An IRAE was suspected in both cases due to a temporal relationship between ICI initiation and symptom onset. ICIs were stopped, and high-dose prednisone, inhaled corticosteroids, and bronchodilators were administered, allowing a rapid clinical and functional improvement in Patient 1. In Patient 2, despite prolonged high-dose prednisone, only a stabilization of forced expiratory volume in 1 s could be achieved, and the disease course was complicated by respiratory infections resulting in further loss of lung function. The patient died 1 year later due to progression of metastatic disease. These 2 cases suggest that pulmonary IRAEs secondary to ICIs may present as isolated bronchitis or bronchiolitis, with variable outcomes following ICI withdrawal and systemic corticosteroids.

Résumé. Une fonction pulmonaire réduite s’associe à une mortalité accrue. La prévalence de troubles respiratoires fonctionnels dépend de sa définition, des références employées et de l’utilisation ou non de bronchodilatateur. Dans l’étude PneumoLaus, conduite entre 2014 et 2017 dans un échantillon de la population de Lausanne, la prévalence d’obstruction chronique était de 3,8 %, d’obstruction réversible de 2,5 % et de possible restriction de 2,2 %, proportions plus basses que dans d’autres études populationnelles. Les hommes présentaient plus souvent des anomalies spirométriques comparé aux femmes et les fumeurs plus souvent que les non-fumeurs. Deux tiers des sujets avec obstruction chronique, pour la plupart sans symptômes respiratoires, ne se connaissaient pas de maladie pulmonaire.

No abstract available.

Introduction: Emerging evidence suggests that long-term pulmonary symptoms and functional impairment occurs in a proportion of individuals following SARS-CoV-2 infection. Although the proportion of affected patients remains to be determined, physicians are increasingly being confronted with patients reporting respiratory symptoms and impairment beyond the acute phase of COVID-19. In face of limited evidence, the Swiss Society for Pulmonology established a working group to address this area of unmet need and formulated diagnostic and treatment recommendations for the care of patients with pulmonary long COVID (LC). Method: The Swiss COVID Lung Study group and Swiss Society for Pulmonology (SSP) formulated 13 questions addressing the diagnosis and treatment of pulmonary LC. A survey within the SSP special interest groups involved in care of LC patients was conducted in Switzerland. A CORE process/Delphi-like process was used to formulate recommendations. Forty experienced pulmonologists replied to the first survey and 22 completed the second follow-up survey. Agreement of ≥70% consensus led to formulation of a recommendation. Results: The participants in the survey reached consensus and formulated a strong recommendation for regarding the following points. Patients hospitalized for COVID-19 should have a pulmonary assessment including pulmonary function tests. Symptomatic subjects affected by COVID-19, including those with mild disease, should benefit from a pulmonary follow-up. Persistent respiratory symptoms after COVID-19 should be investigated by a pulmonary follow-up including plethysmography, diffusion capacity measurement, and blood gases analysis. Individuals having suffered from COVID-19 and who present with persistent respiratory symptoms should be offered a rehabilitation. Additional questions were given moderateor weak recommendations for. The panel did not reach sufficient consensus for pharmacological therapy (e.g., therapy specifically targeting lung fibrosis) to formulate recommendations for LC drug treatment. Conclusion: The formulated recommendations should serve as an interim guidance to facilitate diagnosis and treatment of patients with pulmonary LC. As new evidence emerges, these recommendations may need to be adapted.

OBJECTIVES A lung retransplant has been shown to be a valid option in selected patients with chronic lung allograft dysfunction (CLAD). However, a subgroup of patients may require, in addition to invasive mechanical ventilation, extracorporeal membrane oxygenation (ECMO) as a bridge to a retransplant. Overall and CLAD-free survival after ECMO-bridged retransplants are compared to first transplants with and without bridging ECMO and to retransplants without bridging ECMO. METHODS We reported a retrospective, single-institution experience based on a prospective data set of all patients undergoing lung transplants between January 2004 and December 2016 with a mean follow-up of 51 ± 41 months. RESULTS A total of 230 patients (96 men, 134 women, mean age 47.3 years) had lung transplants: 200 had first transplants without bridging ECMO; 13 had first transplants with bridging ECMO; 11 had retransplants without bridging ECMO; and 6 had retransplants with bridging ECMO. The 3- and 5-year survival rates were 81%/76%, 68%/68%, 69%/46% and 50%/25%, respectively. There was no significant difference in overall survival between those who had first transplants with and without bridging ECMO or retransplants without bridging ECMO. In contrast, patients undergoing ECMO-bridged retransplants had a significantly lower overall survival rate than those with a first transplant without bridging ECMO (P = 0.007). In addition, the post-transplant CLAD-free survival curves varied significantly among the 4 treatment groups (P = 0.041), paralleling overall survival. CONCLUSIONS Patients requiring ECMO as a bridge to a retransplant had lower overall and CLAD-free survival rates compared to those who had a first transplant with and without bridging ECMO and a retransplant without bridging ECMO.

Bei IGRA handelt es sich um In-vitro-Tests zum Nachweis von spezifischen Effektor-T-Lymphozyten, die nach Sensibilisierung durch Mycobacterium tuberculosis Interferon gamma produzieren.

Background: SARS-CoV-2 belongs to a subgroup of coronaviruses rampant in bats for centuries. It has caused the COVID-19 pandemic. Most patients recover, but a minority of severe cases experience acute respiratory distress or an inflammatory storm devastating many organs that can lead to patient death. The spread of SARS-CoV-2 has been facilitated by the increasing intensity of air travel, urban congestion and human contact during the last half century. Until therapies and vaccines are available, tests for virus and exposure, confinement measures and physical distancing have helped curb the pandemic. Vision: The COVID-19 pandemic calls for safeguards and remediation measures through a systemic response. A myriad of self-organizing initiatives by scientists and citizens is developing an advanced collective intelligence response to the coronavirus crisis. Their integration forms Olympiads of Solidarity and Health. Their ability to optimize our response to COVID-19 could serve as a model to trigger a global metamorphosis of our societies with far-reaching consequences for attacking fundamental challenges facing humanity in the 21st century. Mission: For COVID-19 and these other challenges, there is no alternative but action. Meeting in Paris in 2003, we set out to "rethink research to understand life and improve health." We have now formed an international coalition of academia and industry ecosystems taking a systems medicine approach to understanding COVID-19 by thoroughly characterizing viruses, patients and populations during the pandemic, using openly shared tools. All results will be publicly available with no initial claims for intellectual property rights. This World Alliance for Health and Wellbeing will catalyze the creation of medical and health products such as diagnostic tests, drugs and vaccines that become common goods accessible to all, while seeking further alliances with civil society to bridge with socio-ecological and technological approaches that characterise urban systems, for a collective response to future health emergencies. Funding: This work was supported during its preparation phases by the State Key Laboratory of Medical Genomics, Overseas Expertise Introduction Project for Discipline Innovation (111 Project, B17029) to SJC, LH, CA; European Union grants CASyM (FP7-n°305033) to CA, RB, JR, DR, DS, JT, OW; eTRIKS (IMI-1-n°115446) to CA, RB, YG; PREPARE (FP7n°602525) to CA, PO, SV; and initial funds in support of the deep phenotyping clinical study from philanthropic donors, Gilead, Merck and Novartis to JG, JH, LH; the Ricerca Corrente Program by the Italian Ministry of Health to AC, CPr, GS, AU, VV; the National Megaprojects of China for Infectious Diseases (2017ZX10103009-001, 2018ZX10305409-001-005), Double Firstclass projects from the Ministry of Education to the National Research Center for Translational Medicine Shanghai to SJC; Shanghai Municipal Science and Technology Major Project (2017SHZDZX01) to LJ. Conflict of Interest: Rudi Balling reports being a founder/shareholder of ITTM S.A. and Megeno S.A., outside the submitted work, he is co-inventor and holder of two issued patents; James Heath reports personal fees and other from PACT Pharma, outside the submitted work; Hiroaki Kitano reports grants from Minister of Health, Welfare, and Labor of Japanese Government, grants from Okinawa Prefecture Government, outside the submitted work; Doron Lancet reports personal fees from Weizmann Institute of Science and LifeMap Science Inc., outside the submitted work; Catherine Larue reports personal fees from Genfit, outside the submitted work; Peter Openshaw reports personal fees for consultancy work with Janssen, JJ Susanna Palkonen reports grants from Aimmune, Astra Zeneca, Boehringer Ingelheim, Chiesi, DBV Technologies, GSK, Leo Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, outside the submitted work, is employed by the EFA who receives unrestricted grants from corporate entities as above, represents EFA in the following advisory groups of these entities: Astra Zeneca COPD Advisory Committee, GSK Health Advisory Board and Novartis European Patient Advisory Group, receives no personal gain, honoraria, when applicable expenses are payed to her organization, is in a voluntary function the Chair of the Patient Access Partnership PACT who receives unrestricted grants from EFPIA, MedTech Europe, EUCOPE and Medicines for Europe for core operations, and project grants from individual companies, outside the submitted work; Christophe Pison reports personal fees and non-financial support from AstraZeneca, Boehringer Ingelheim, GSK, Novartis, outside the submitted work; Mihael Polymeropulos reports other from Vanda Pharmaceuticals, outside the submitted work; Ulrike Protzer reports grants from VIR Biotechnology, grants and non-financial support from Roche, grants from Alios-JJ Peter Sterk reports other from Breathomix BV, outside the submitted work; Giulio Superti-Furga reports being a shareholder of Proxygen GmbH, Haplogen GmbH and Allcyte GmbH, outside the submitted work; Vincenzo Valentini reports personal fees from Merck Serono, Betaglue, outside the submitted work; Sylvie van der Werf reports other from Sanofi Pasteur, outside the submitted work; she is the holder of four issued patents. The other authors have declared no conflict of interest.

Mental health disorders figure among the many comorbidities of chronic obstructive pulmonary diseases.The purpose of this study is to evaluate the association of airway obstruction with mental disorders in the Swiss general population. PneumoLaus is based on the CoLaus|PsyCoLaus cohort inluding spirometry and a semi-structured interview on mental health in a random sample of the Lausanne general population(Switzerland).We defined reversible obstruction(RO) as FEV1/FVC LLN or FVC>LLN after bronchodilation(BD). Chronic obstruction(CO) was defined as FEV1/FVC In total, 2774 subjects performed spirometry and were assessed through the PsyCoLaus interview. We found evidence for associations of self-reported doctor-diagnosed asthma (OR 1.60, 95%CI 1.06–2.39) and COPD, emphysema or chronic bronchitis(OR 2.61, 95%CI 1.19–5.71) with recent remitted or current major depression(RCD). These associations were not found when spirometric criteria(CO, RO, FEV1, FVC in % predicted) were used instead of the self-reported diagnoses. There was some suggestion for associations between RO and RCD(OR 1.62, 95%CI 0.87-3.01) and RO and recent remitted/current anxiety disorder(OR 1.95, 95%CI 0.99–3.87). Subjects with known diagnosis of obstructive respiratory disease more frequently suffer from depression and anxiety. However, this association was not confirmed when using objective spirometric values instead of self-reported diagnoses.

There is accumulating evidence that the lower airway microbiota impacts lung health. However, the link between microbial community composition and lung homeostasis remains elusive. We combine amplicon sequencing and bacterial culturing to characterize the viable bacterial community in 234 longitudinal bronchoalveolar lavage samples from 64 lung transplant recipients and establish links to viral loads, host gene expression, lung function, and transplant health. We find that the lung microbiota post-transplant can be categorized into four distinct compositional states, ‘pneumotypes’. The predominant ‘balanced’ pneumotype is characterized by a diverse bacterial community with moderate viral loads, and host gene expression profiles suggesting immune tolerance. The other three pneumotypes are characterized by being either microbiota-depleted, or dominated by potential pathogens, and are linked to increased immune activity, lower respiratory function, and increased risks of infection and rejection. Collectively, our findings establish a link between the lung microbial ecosystem, human lung function, and clinical stability post-transplant., Here, the authors combine 16 S rRNA sequencing, culture and bioinformatics to profile the microbiome in 234 serial bronchoalveolar lavage samples from 64 lung transplant recipients collected over 49-months and identify distinct compositional states, termed pneumotypes, linked to current health status, and establish a collection of primary lung bacterial isolates, LuMiCol.

A combination of targeted molecular methods and phenotypic drug-susceptibility testing is the most widely used approach to detect drug resistance in Mycobacterium tuberculosis isolates. We report the delay in the introduction of an efficient anti-tuberculous drug regimen because of a M. tuberculosis strain displaying a high level of resistance to isoniazid, in the absence of the common mutations associated with isoniazid-resistance, including katG mutations and inhA promoter mutations. Whole-genome sequencing (WGS) identified a large loss-of-function insertion (>1000 pb) at the end of katG in the isolate together with a -57C>T ahpC mutation, a resistance mechanism that would have remained undetected by a conventional molecular targeted approach. A retrospective search using publicly available WGS data of more than 1200 isoniazid-resistant isolates and a similar sized control dataset of isoniazid-susceptible isolates revealed that most (22/31) isoniazid-resistant, KatG loss-of-function mutants had an associated rare ahpC promoter mutation. In contrast, only 7 of 1411 isoniazid-susceptible strains carried a rare ahpC promoter mutation, including shared mutations with the 31 isoniazid-resistant KatG loss-of-function mutants. These results indicate that rare ahpC promoter mutations could be used as a proxy for investigating simultaneous KatG loss-of-function or missense mutations. In addition, WGS in routine diagnosis would improve drug susceptibility testing in M. tuberculosis clinical isolates and is an efficient tool for detecting resistance mechanisms undetected by conventional molecular methods.

The Global Initiative for Asthma (GINA) is a network of individuals, organizations, and public health officials that was established to disseminate information about the care of patients with asthma and to improve asthma care. The GINA (“Global Strategy for Asthma Management and Prevention”) report has been updated annually since 2002. Due to new knowledge and therapeutic development in the field, the Swiss Respiratory Society felt the need to provide a new document that is based on both the available literature and the recommendations of the 2016 GINA report. Key new features of the 2016 GINA report include a “new” definition of asthma, underscoring its heterogeneous nature, and the core elements of variable symptoms and variable expiratory airflow limitation; the importance of confirming the diagnosis of asthma in order to minimize both under- and overtreatment; practical tools for the assessment of symptom control and risk factors for adverse outcomes; a comprehensive approach to asthma management that acknowledges the foundational role of inhaled corticosteroid therapy, but also provides a framework for individualizing patient care; an emphasis on maximizing the benefit of available medications by addressing common problems such as incorrect inhaler technique and poor adherence; a continuum of care for worsening asthma, starting with early self-management and progressing to primary care or acute care management; and diagnosis of the asthma/chronic obstructive pulmonary disease overlap syndrome. This document is meant to advice the key stakeholders on the diagnosis and management of asthma and highlights the need to individualize the care of each and every asthmatic patient.

Significant iatrogenic bleeding during flexible bronchoscopy is fortunately rare and usually self-limiting. Life-threatening bleeding, however, can occur, especially after conventional or cryoprobe-assisted transbronchial biopsy. The aim of this review is to provide the practising pulmonologist with a concise overview of the incidence, severity and risk factors for bleeding, to provide sensible advice on prophylactic measures and to suggest a plan of action in the case of significant bleeding. Bronchoscopy units should have a standardised approach and plan of action in the case of life-threatening haemorrhage. Wedging the bronchoscope in the bleeding segment, turning the patient in an anti-Trendelenburg position and onto the side in order for the bleeding lung to be in the dependent position, installing vasoconstrictors and using a tamponade balloon early are the recommended first-line strategies. Involving a resuscitation team should be considered early in the case of massive bleeding, desaturation and haemodynamic instability., Iatrogenic bleeding during flexible bronchoscopy http://ow.ly/w9Fy30bsoe5

Cystic lung diseases constitute a distinct group of rare lung disorders, among which two result from monogenic defects affecting tumor suppressor genes: lymphangioleiomyomatosis, either sporadic or associated with tuberous sclerosis complex, and Birt-Hogg-Dubé syndrome. These disorders have similarities in their clinical expression, including occurrence in young adults, multiple pulmonary cysts, recurrent pneumothorax, skin hamartomas, and renal tumors. However, they markedly differ in their gender distribution, pathogenesis, disease course, and prognosis. Our knowledge on these two rare conditions is rapidly expanding. Management of lymphangioleiomyomatosis has substantially improved in the past decade with the understanding of its pathogenic mechanisms, the discovery of an effective therapy, and development of large cohorts and international guidelines. Birt-Hogg-Dubé syndrome has been described more recently and still awaits deeper understanding of its pathophysiology.

The diagnosis of mycobacterial infections has been dramatically improved by the introduction of molecular methods aimed to reduce the time to diagnosis as compared with culture. The broad range pan-mycobacterial PCR can detect all the mycobacterial species directly from clinical specimens. We aimed to evaluate its usefulness and its clinical added value for the diagnosis of nontuberculous mycobacterial (NTM) infections. We performed a retrospective study (2003–2013) including 952 samples taken from 639 patients with clinical suspicion of NTM infection. The performance of smear microscopy, PCR and culture was established using clinical data to investigate discrepant results. We also compared the time to microbial diagnosis between the direct PCR and culture. The sensitivity, specificity, positive and negative predictive values of the PCR were 61.6% (53.5–69.1), 99.1% (98.2–99.6), 92.8% (85.8–96.5) and 93.4% (91.6–94.9), respectively, when considering all specimens. When considering smear-positive specimens and smear-negative specimens, the sensitivity was 81.6% and 40%, respectively. The sensitivity for pulmonary and extra-pulmonary smear-positive specimens was 85.2% versus 72.7%. The median time to identification at species level was 35 days (SD, 17.67) for culture and 6 days (SD, 2.67) for the PCR (when positive), which represents a 29-day shorter time to results (p

Introduction: Low density bacterial communities reside in the lower airways, however the importance of their stability for complication-free survival after lung transplantion (Tx) is poorly understood. Aims:i) To identify the most common and abundant members of the bacterial lung microbiota post-Tx, and ii) to explore whether disruption of this core community is linked to clinical complications. Methods: We prospectively analyzed 234 serial bronchoalveolar lavage (BAL) samples from 64 recipients up to 49 months post-Tx, using 16S quantification and sequencing. Unsupervised clustering was used to differentiate bacterial communities. Cell differentials were obtained for paired BAL and blood samples. Post-Tx clinical complications were sought from patient charts. Results: The most common and abundant operational taxonomic units, mapping to the genera Prevotella, Streptococcus and Veillonella, were linked to a single cluster that identified the core lung microbiota. We further observed two divergent bacterial communities linked to contrasting clinical pictures. Compared with the core, median differences in the first sample set were a 46-fold lower bacterial load, 2.7-fold higher blood lymphocyte counts, and a 3.3-fold higher rate of either acute rejection, chronic lung allograft dysfunction or presence of donor-specific antibodies, while those in the second set were a 2.6-fold lower diversity, 4-fold higher BAL neutrophil counts, and a 3.3-fold higher infection rate. Conclusions: Complication-free survival post-lung Tx is tied to a stable core microbiota, the disruption of which is related to sub-control (rejection) or excessive control (infection) of host immunity.

Skin allergen sensitization can induce atopic dermatitis (AD), which is considered the starting point of the ‘atopic march’. The ‘atopic march’ is the progression of AD in infancy to allergic rhinitis and allergic asthma in childhood. We hypothesize that the skin microbiome drives immune maturation, and that the maturation state at the time of skin allergen sensitization determines the allergic airway inflammation phenotype following allergen challenge. Neonatal and adult mice were subjected to a 3-week epicutaneous allergen sensitization protocol followed by intranasal allergen challenges. Skin and lung tissue inflammation was assessed using histological and FACS analysis. Skin transcriptome and microbiome was analyzed using RNA-seq and 16S rRNA sequencing. The immune maturation state at the time of first sensitization determines a Th2 vs. a mixed Th2/Th17 driven allergic inflammation in both the skin and the lung. Naive neonatal mouse skin exhibited decreased antigen presenting cell frequencies and a decreased antigen uptake and processing capacity compared to adults. Transcriptome analysis revealed that genes associated with immune response and bacterial response pathways were enriched in adult skin compared to neonatal skin. Similar genes were downregulated in adult germ-free mouse skin, suggesting an important role for the microbiome. Epicutaneous allergen sensitization in adult mice was characterized by increased Staphylococcus aureus abundance on the skin, and neutrophil accumulation and increased IL17 gene expression in both the skin and the lung. Taken together, the skin microbiome drives immune maturation and exacerbation of both skin and airway inflammation.

Contact investigations following the diagnosis of active tuberculosis (TB) are paramount for the control of the disease. Epidemiological data are very powerful for contact tracing but might be delayed and/or difficult to integrate, especially in the setting of multiple contact-tracing investigations. The aim of this study was to address the added-value of whole-genome sequencing (WGS) to routine local TB surveillance systems. From November 2016 to July 2017, the local TB surveillance system identified three clusters that could constitute a unique larger outbreak. Epidemiological and clinical information were integrated with WGS genotyping data of Mycobacterium tuberculosis strains obtained using a simple DNA extraction method coupled with sequencing using an Illumina MiSeq platform and an in-house bioinformatics pipeline for single nucleotide polymorphism (SNP) analysis. Epidemiological investigations identified three putative TB clusters potentially interrelated including eight patients with active TB. Seven M. tuberculosis isolates were available and analysed by WGS. Using a 5-SNP threshold to define recent transmission, WGS-based genotyping supported the occurrence of the three clusters as well as a link between clusters 1 and 2 (SNP ≤1), constituting a larger outbreak. This outbreak was clearly delineated by refuting a potential link with the third cluster (SNP >500). Genotyping data did not support the belonging of patient 7 to any studied cluster. This study illustrates the usefulness of WGS genotyping for routine TB surveillance systems in local communities to rapidly confirm or disprove epidemiological hypotheses and delineate TB clusters, especially in the context of multiple contact-tracing investigations. Keywords: Contact investigation, genotyping outbreak, molecular epidemiology, Mycobacterium tuberculosis, whole-genome sequencing

Skin allergen sensitization can induce atopic dermatitis (AD), which is considered the starting point of the ‘atopic march’. The ‘atopic march’ is the progression of AD in infancy to allergic rhinitis and allergic asthma in childhood. We hypothesize that the skin microbiome drives immune maturation, and that the maturation state at the time of skin allergen sensitization determines the allergic airway inflammation phenotype following allergen challenge. Neonatal and adult mice were subjected to a 3-week epicutaneous allergen sensitization protocol followed by intranasal allergen challenges. Skin and lung tissue inflammation was assessed using histological and FACS analysis. Skin transcriptome and microbiome was analyzed using RNA-seq and 16S rRNA sequencing. The immune maturation state at the time of first sensitization determines a Th2 vs. a mixed Th2/Th17 driven allergic inflammation in both the skin and the lung. Naive neonatal mouse skin exhibited decreased antigen presenting cell frequencies and a decreased antigen uptake and processing capacity compared to adults. Transcriptome analysis revealed that genes associated with immune response and bacterial response pathways were enriched in adult skin compared to neonatal skin. Similar genes were downregulated in adult germ-free mouse skin, suggesting an important role for the microbiome. Epicutaneous allergen sensitization in adult mice was characterized by increased Staphylococcus aureus abundance on the skin, and neutrophil accumulation and increased IL17 gene expression in both the skin and the lung. Taken together, the skin microbiome drives immune maturation and exacerbation of both skin and airway inflammation.

Background Reduced lung function predicts increased mortality, but its prevalence may vary depending on definition considered, use of bronchodilation and applied reference values. We aimed to assess lung function abnormalities in Lausanne, Switzerland, and their association with clinical history. Methods In a general population sample, spirometry was performed and bronchodilation applied if the ratio forced expiratory volume in 1 s (FEV1) / forced vital capacity (FVC) or the FVC was below the lower limit of normal (LLN) according to Global Lung Function Initiative 2012 references. Results for FEV1/FVC according to the LLN were compared to the 0.7 fixed ratio. Respiratory risk factors, symptoms and self-reported respiratory diagnoses were recorded through a questionnaire. Results Out of the 3342 included subjects, 3.8% had chronic obstruction and 2.5% reversible obstruction when using the LLN; possible lung restriction alone was present in 1.8%, and associated with chronic obstruction in 0.4%. Ever smokers had a higher prevalence of abnormal spirometry, chronic obstruction and reversible obstruction; there was no difference with regard to possible restriction. Overall, chronic airway obstruction was found in 8.9% of current smokers, 4.6% of former smokers and 1.5% of never smokers. Only one third of participants with chronic obstruction were aware of a respiratory disease. Conclusion Prevalence of abnormal lung function in the population of Lausanne is low. This may be due to a low rate of ever-smokers, the application of a full bronchodilation dose, but also to inherent characteristics of this population.

Background Allergic skin inflammation often presents in early childhood; however, little is known about the events leading to its initiation and whether it is transient or long-term in nature. Objective We sought to determine the immunologic rules that govern skin inflammation in early life. Methods Neonatal and adult mice were epicutaneously sensitized with allergen followed by airway allergen challenge. Epicutaneous application of labeled allergen allowed for determination of antigen uptake and processing by antigen-presenting cells. RNAseq and microbiome analysis was performed on skin from neonatal and adult specific pathogen-free and germ-free mice. Results A mixed TH2/TH17 inflammatory response in the skin and the lungs of adult mice was observed following sensitization and challenge. Comparatively, neonatal mice did not develop overt skin inflammation, but exhibited systemic release of IL-17a and a TH2-dominated lung response. Mechanical skin barrier disruption was not sufficient to drive allergic skin inflammation, although it did promote systemic immune priming. Skin of neonatal mice and adult germ-free mice was seeded with low numbers of antigen-presenting cells and impaired chemokine and alarmin production. Enhanced chemokine and alarmin production, and seeding of the skin with antigen-presenting cells capable of instructing recruited cells to elicit their effector function, was, at least in part, dependent on formation of the microbiome, and consequently contributed to the development of overt skin disease. Conclusions These data shed light on the principles that underlie allergic inflammation in different tissues and highlight a window of opportunity that might exist for early-life prevention of allergic diseases.

The role of radial-endobronchial ultrasound (R-EBUS) assisted transbronchial biopsy (TBB) for the diagnosis of peripheral pulmonary lesions is well established. However, no study has addressed its safety and value in hemato-oncological patients presenting with non-resolving infiltrates during persistent febrile neutropenia. To assess safety and feasibility of R-EBUS assisted TBB in severe thrombocytopenic and neutropenic patients. Over a period of 18 months, eight patients were assessed with R-EBUS assisted TBB after adequate platelet transfusion. This technique allowed precise localisation and sampling of the pulmonary lesions in seven of eight patients. In the seven patients, R-EBUS assisted TBB enabled treatment optimization. Invasive fungal infection was diagnosed in four patients, idiopathic acute fibrinous and organising pneumonia in three patients, and a granulomatous inflammation of undetermined origin in one patient. Importantly, no complications, such as bleeding, were observed. R-EBUS assisted TBB is a promising and safe procedure for the evaluation of nonresolving pulmonary infiltrates in febrile neutropenic hemato-oncological patients.

Ochroconis gallopava is an anamorphic mould characterized by slow growth rate and production of a maroon pigment, which has been isolated worldwide from soil, thermal springs, decaying vegetation, and chicken litter. It has been reported to cause localized, mostly pulmonary, and systemic infection in severely immunocompromised patients. We describe the case of a 76-year-old woman known for ulcerative colitis-related bronchiectasis treated with low dose oral steroids, who developed a fungal bronchitis with dark, bloody-like, sputum which was initially misinterpreted as haemoptysis. A filamentary mould grew on sputum culture, and was identified by DNA analysis as Ochroconis gallopava . We observed a significant clinical improvement after 6 weeks of itraconazole therapy.

Respiratory tract infections represent a major cause of morbidity and mortality despite the progress made in their diagnosis and treatment. Since the clinical presentation of a viral or bacterial infection is often similar, the identification of a biomarker that could guide the clinician whether or not to introduce an antibiotic therapy is crucial. C-reactive protein and procalcitonin are the most commonly used biomarkers as a diagnostic tool for respiratory tract infections. New biomarkers show promising results for assessing the severity of infection and identifying patients at risk for complications. However, the use of biomarkers has limitations and the diagnosis of a bacterial infection should not be based solely on the measurement of a biomarker.Malgré le progrès effectué pour le diagnostic et le traitement des infections respiratoires, ces dernières représentent une cause de morbidité et mortalité importante. La présentation clinique d’une infection virale ou bactérienne étant souvent identique, l’identification d’un biomarqueur qui pourrait aider le clinicien à la décision d’introduire ou pas un traitement antibiotique est cruciale. La protéine C-réactive et la procalcitonine sont les biomarqueurs les plus fréquemment utilisés comme aide au diagnostic. Des nouveaux biomarqueurs montrent des résultats prometteurs pour évaluer la sévérité de l’infection et les patients à risque de complication. Toutefois, l’utilisation des biomarqueurs présente des limitations et le diagnostic d’une infection bactérienne ne doit en aucun cas être basé uniquement sur la mesure d’un biomarqueur.

Chronic hypercapnic respiratory failure is essentially a ventilatory failure. Noninvasive ventilation (NIV ) reduces the work of breathing, improves pulmonary compliance and alveolar ventilation, corrects gas exchange disorders and improves dyspnoea. However, treatment efficacy depends on the underlying pathology, on correct timing and on patient compliance. In this context, the principal role of the primary care physician is to search for, at every visit of at risk patients, signs and symptoms of ventilatory failure and to refer the patient to a respiratory care specialist. He also plays a role in the follow up of patients under noninvasive ventilation for the detection of clinical parameters suggesting NIV failure.L’insuffisance respiratoire hypercapnique chronique est essentiellement une défaillance ventilatoire. La ventilation non invasive (VNI) diminue le travail des muscles respiratoires, augmente la compliance thoracique, améliorant ainsi la dyspnée et les troubles des échanges gazeux. Toutefois, l’efficacité du traitement dépend de la pathologie sous-jacente, du bon timing d’initiation et de la compliance du patient. Dans ce contexte, le rôle principal du médecin de premier recours consiste à rechercher, lors de chaque visite médicale de patients à risque, des signes et symptômes de défaillance ventilatoire qui nécessitent de référer le patient à un pneumologue. Son rôle est aussi important dans le suivi des patients ventilés pour la détection précoce des paramètres cliniques suggérant un échec de VNI.

Aufgrund der hohen Mortalitat bei Nichtbehandlung sind sowohl bei akuter als auch chronischer Entzundung des Mediastinums eine rasche Diagnosestellung und Behandlung erforderlich.

L’inflammation du mediastin, qu’elle soit aigue ou chronique, necessite un diagnostic et une intervention rapide, en raison de la mortalite elevee en absence de traitement.