One-year persistent symptoms and functional impairment in SARS-CoV-2 positive and negative individuals.

BACKGROUND: Persistent symptoms of SARS-CoV-2 are prevalent weeks to months following the infection. To date, it is difficult to disentangle the direct from the indirect effects of SARS-CoV-2, including lockdown, social, and economic factors. OBJECTIVE: The study aims to characterize the prevalence of symptoms, functional capacity, and quality of life at 12 months in outpatient symptomatic individuals tested positive for SARS-CoV-2 compared to individuals tested negative. METHODS: From 23 April to 27 July 2021, outpatient symptomatic individuals tested for SARS-CoV-2 at the Geneva University Hospitals were followed up 12 months after their test date. RESULTS: At 12 months, out of the 1447 participants (mean age 45.2 years, 61.2% women), 33.4% reported residual mild to moderate symptoms following SARS-CoV-2 infection compared to 6.5% in the control group. Symptoms included fatigue (16% vs. 3.1%), dyspnea (8.9% vs. 1.1%), headache (9.8% vs. 1.7%), insomnia (8.9% vs. 2.7%), and difficulty concentrating (7.4% vs. 2.5%). When compared to the control group, 30.5% of SARS-CoV-2 positive individuals reported functional impairment at 12 months versus 6.6%. SARS-CoV-2 infection was associated with the persistence of symptoms (adjusted odds ratio [aOR] 4.1; 2.60-6.83) and functional impairment (aOR 3.54; 2.16-5.80) overall, and in subgroups of women, men, individuals younger than 40 years, those between 40-59 years, and in individuals with no past medical or psychiatric history. CONCLUSION: SARS-CoV-2 infection leads to persistent symptoms over several months, including in young healthy individuals, in addition to the pandemic effects, and potentially more than other common respiratory infections. Symptoms impact functional capacity up to 12 months post infection.

[Pulmonology 2021: year in review]. / Pneumologie.

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.

Parmi les nouveautés thérapeutiques en pneumologie au cours de l'année 2021, nous aborderons trois sujets. Une nouvelle biothérapie est désormais disponible pour la prise en charge de l'asthme sévère non contrôlé non T-Helper 2. Concernant l'hypertension artérielle pulmonaire (HTAP), une triple thérapie d'emblée au moment du diagnostic est associée à un bénéfice sur la survie chez les patients à haut risque. Le riociguat est une option thérapeutique lors d'HTAP restant à risque intermédiaire malgré un traitement par inhibiteur de la phosphodiestérase de type 5, et le sotatercept vise une nouvelle cible thérapeutique prometteuse pour l'HTAP du groupe 1. Enfin, la place des cryobiopsies transbronchiques comme alternative valable à la biopsie chirurgicale pour le diagnostic des pneumopathies interstitielles diffuses selon des recommandations récentes se précise.

Burden, epidemiology, and outcomes of microbiologically confirmed respiratory viral infections in solid organ transplant recipients: a nationwide, multi-season prospective cohort study.

Solid organ transplant (SOT) recipients are exposed to respiratory viral infection (RVI) during seasonal epidemics; however, the associated burden of disease has not been fully characterized. We describe the epidemiology and outcomes of RVI in a cohort enrolling 3294 consecutive patients undergoing SOT from May 2008 to December 2015 in Switzerland. Patient and allograft outcomes, and RVI diagnosed during routine clinical practice were prospectively collected. Median follow-up was 3.4 years (interquartile range 1.61-5.56). Six hundred ninety-six RVIs were diagnosed in 151/334 (45%) lung and 265/2960 (9%) non-lung transplant recipients. Cumulative incidence was 60% (95% confidence interval [CI] 53%-69%) in lung and 12% (95% CI 11%-14%) in non-lung transplant recipients. RVI led to 17.9 (95% CI 15.7-20.5) hospital admissions per 1000 patient-years. Intensive care unit admission was required in 4% (27/691) of cases. Thirty-day all-cause case fatality rate was 0.9% (6/696). Using proportional hazard models we found that RVI (adjusted hazard ratio [aHR] 2.45; 95% CI 1.62-3.73), lower respiratory tract RVI (aHR 3.45; 95% CI 2.15-5.52), and influenza (aHR 3.57; 95% CI 1.75-7.26) were associated with graft failure or death. In this cohort of SOT recipients, RVI caused important morbidity and may affect long-term outcomes, underlying the need for improved preventive strategies.

Swiss Recommendations for the Follow-Up and Treatment of Pulmonary Long COVID.

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.

[Diagnostic approach to pulmonary complications in patients with hematologic malignancy]. / Approche diagnostique des complications pulmonaires chez les patients avec une hémopathie maligne.

Hematologic malignancies are heterogeneous group of neoplasia, with frequent pulmonary complications. These complications may be secondary to the patient's comorbidities, to the hemopathy itself or its treatments. Divided into infectious and non-infectious complications, the etiologies are numerous and varied. This makes the diagnostic approach complex for the clinicians. A structured decision-making process, based on the development of diagnostic hypotheses, is essential. Given the vulnerability of the patients, the diagnostic approach must be rapid, using all available diagnostic tools. Knowledge of the indications and limitations of these tests is therefore essential.

Les hémopathies malignes sont un groupe hétérogène de néoplasies, aux complications pulmonaires fréquentes. Ces complications peuvent être secondaires aux comorbidités du patient, à l'hémopathie et/ou à son traitement. Réparties en complications infectieuses et non infectieuses, les étiologies sont nombreuses, variées et fréquemment associées. Ceci rend l'approche diagnostique complexe pour le clinicien. Un processus décisionnel structuré, basé sur l'élaboration d'hypothèses diagnostiques est indispensable. Compte tenu de la précarité des patients, cette approche diagnostique doit être rapide en utilisant l'ensemble de l'arsenal diagnostique disponible. Une connaissance des indications et des limites de ces tests est alors indispensable.

[Pulmonary telerehabilitation†: a new standard†?] / Télé-réhabilitation pulmonaire†: un nouveau standard†?

Pulmonary rehabilitation is effective to improve shortness of breath, health status and exercise capacity. Telerehabilitation uses information and communication technologies to deliver rehabilitation program from a distance. A Cochrane review published in 2021 shows its equivalence to conventional pulmonary rehabilitation. The confinement induced by the COVID-19 pandemic has made patients with respiratory failure even more fragile and vulnerable, promoting the development of telerehabilitation. This article describes its modalities, sets out the scientific evidence for its effectiveness and develops perspectives for its development.

La réhabilitation pulmonaire est efficace pour réduire les symptômes, améliorer l'état de santé et la capacité d'effort. La télé-réhabilitation utilise les technologies de l'information et de la communication pour dispenser des activités de réhabilitation à distance. Une revue Cochrane parue en 2021 montre son équivalence à la réhabilitation pulmonaire conventionnelle. Le confinement induit par la pandémie de Covid-19 a rendu les patients avec insuffisance respiratoire encore plus fragiles et vulnérables, favorisant le développement de la télé-réhabilitation. Cet article en décrit les modalités, énonce les preuves scientifiques de son efficacité et propose des perspectives quant à son développement.

[Lung cancer screening in Switzerland†: Who†? How†? When†?] / Dépistage du cancer pulmonaire en Suisse†: Qui†? Comment†? Quand†?

Professional societies encourage the establishment of coordinated national screening programs for lung cancer by «â€…low-dose ¼ chest CT scans. The interdisciplinary Swiss Lung Cancer Screening Implementation Group (CH-LSIG) is exploring the feasibility of such a project. However, several questions still remain unanswered, namely the -financing of such a program, the ideal «â€…number-needed to screen ¼, the definition and follow-up of «â€…positive cases ¼, as well as the role of smoking cessation measures. The key points to discuss in the future with patients requesting screening are based on the «â€…shared -decision-making ¼ approach. Pilot projects guided by the CH-LSIG could help to identify the optimal strategy for establishing a national screening program based on the best available scientific evidence.

Les sociétés savantes encouragent le développement de programmes nationaux de dépistage du cancer pulmonaire par CT-scan thoracique low-dose. En Suisse, le groupe de travail ­interdisciplinaire Swiss Lung Cancer Screening Implementation Group (CH-LSIG) s'emploie à la mise en œuvre d'un tel projet. Néanmoins, de nombreuses questions demeurent encore ouvertes, portant sur le financement d'un tel programme, le Number ­Needed to Screen idéal, la définition des «â€…cas positifs ¼ et l'intégration optimale des mesures de sevrage tabagique. Le concept de décision médicale partagée servira de modèle pour répondre aux futurs patients demandeurs d'un examen de dépistage. Des projets pilotes guidés par le CH-LSIG pourraient permettre d'identifier la stratégie la plus performante afin d'implémenter un programme fondé sur les preuves.

Usefulness of a systematic approach at listing for vaccine prevention in solid organ transplant candidates.

Solid organ transplant (SOT) candidates may not be immune against potentially vaccine-preventable diseases because of insufficient immunizations and/or limited vaccine responses. We evaluated the impact on vaccine immunity at transplant of a systematic vaccinology workup at listing that included (1) pneumococcal with and without influenza immunization, (2) serology-based vaccine recommendations against measles, varicella, hepatitis B virus, hepatitis A virus, and tetanus, and (3) the documentation of vaccines and serology tests in a national electronic immunization registry (www.myvaccines.ch). Among 219 SOT candidates assessed between January 2014 and November 2015, 54 patients were transplanted during the study. Between listing and transplant, catch-up immunizations increased the patients' immunity from 70% to 87% (hepatitis A virus, P = .008), from 22% to 41% (hepatitis B virus, P = .008), from 77% to 91% (tetanus, P = .03), and from 78% to 98% (Streptococcus pneumoniae, P = .002). Their immunity at transplant was significantly higher against S. pneumoniae (P = .006) and slightly higher against hepatitis A virus (P = .07), but not against hepatitis B virus, than that of 65 SOT recipients transplanted in 2013. This demonstrates the value of a systematic multimodal serology-based approach of immunizations of SOT candidates at listing and the need for optimized strategies to increase their hepatitis B virus vaccine responses.

Genetic immune and inflammatory markers associated with diabetes in solid organ transplant recipients.

New-onset diabetes mellitus after transplantation (NODAT) is a complication following solid organ transplantation (SOT) and may be related to immune or inflammatory responses. We investigated whether single nucleotide polymorphisms (SNPs) within 158 immune- or inflammation-related genes contribute to NODAT in SOT recipients. The association between 263 SNPs and NODAT was investigated in a discovery sample of SOT recipients from the Swiss Transplant Cohort Study (STCS, n1  = 696). Positive results were tested in a first STCS replication sample (n2  = 489) and SNPs remaining significant after multiple test corrections were tested in a second SOT replication sample (n3  = 156). Associations with diabetic traits were further tested in several large general population-based samples (n > 480 000). Only SP110 rs2114592C>T remained associated with NODAT in the STCS replication sample. Carriers of rs2114592-TT had 9.9 times (95% confidence interval [CI]: 3.22-30.5, P = .00006) higher risk for NODAT in the combined STCS samples (n = 1184). rs2114592C>T was further associated with NODAT in the second SOT sample (odds ratio: 4.8, 95% CI: 1.55-14.6, P = .006). On the other hand, SP110 rs2114592C>T was not associated with diabetic traits in population-based samples, suggesting a specific gene-environment interaction, possibly due to the use of specific medications (ie, immunosuppressants) in transplant patients and/or to the illness that may unmask the gene effect.

Genetic and clinic predictors of new onset diabetes mellitus after transplantation.

New Onset Diabetes after Transplantation (NODAT) is a frequent complication after solid organ transplantation, with higher incidence during the first year. Several clinical and genetic factors have been described as risk factors of Type 2 Diabetes (T2DM). Additionally, T2DM shares some genetic factors with NODAT. We investigated if three genetic risk scores (w-GRS) and clinical factors were associated with NODAT and how they predicted NODAT development 1 year after transplantation. In both main (n = 725) and replication (n = 156) samples the clinical risk score was significantly associated with NODAT (ORmain: 1.60 [1.36-1.90], p = 3.72*10-8 and ORreplication: 2.14 [1.39-3.41], p = 0.0008, respectively). Two w-GRS were significantly associated with NODAT in the main sample (ORw-GRS 2:1.09 [1.04-1.15], p = 0.001 and ORw-GRS 3:1.14 [1.01-1.29], p = 0.03) and a similar ORw-GRS 2 was found in the replication sample, although it did not reach significance probably due to a power issue. Despite the low OR of w-GRS on NODAT compared to clinical covariates, when integrating w-GRS 2 and w-GRS 3 in the clinical model, the Area under the Receiver Operating Characteristics curve (AUROC), specificity, sensitivity and accuracy were 0.69, 0.71, 0.58 and 0.68, respectively, with significant Likelihood Ratio test discrimination index (p-value 0.0004), performing better in NODAT discrimination than the clinical model alone. Twenty-five patients needed to be genotyped in order to detect one misclassified case that would have developed NODAT 1 year after transplantation if using only clinical covariates. To our knowledge, this is the first study extensively examining genetic risk scores contributing to NODAT development.

Airway microbiota signals anabolic and catabolic remodeling in the transplanted lung.

BACKGROUND: Homeostatic turnover of the extracellular matrix conditions the structure and function of the healthy lung. In lung transplantation, long-term management remains limited by chronic lung allograft dysfunction, an umbrella term used for a heterogeneous entity ultimately associated with pathological airway and/or parenchyma remodeling. OBJECTIVE: This study assessed whether the local cross-talk between the pulmonary microbiota and host cells is a key determinant in the control of lower airway remodeling posttransplantation. METHODS: Microbiota DNA and host total RNA were isolated from 189 bronchoalveolar lavages obtained from 116 patients post lung transplantation. Expression of a set of 11 genes encoding either matrix components or factors involved in matrix synthesis or degradation (anabolic and catabolic remodeling, respectively) was quantified by real-time quantitative PCR. Microbiota composition was characterized using 16S ribosomal RNA gene sequencing and culture. RESULTS: We identified 4 host gene expression profiles, among which catabolic remodeling, associated with high expression of metallopeptidase-7, -9, and -12, diverged from anabolic remodeling linked to maximal thrombospondin and platelet-derived growth factor D expression. While catabolic remodeling aligned with a microbiota dominated by proinflammatory bacteria (eg, Staphylococcus, Pseudomonas, and Corynebacterium), anabolic remodeling was linked to typical members of the healthy steady state (eg, Prevotella, Streptococcus, and Veillonella). Mechanistic assays provided direct evidence that these bacteria can impact host macrophage-fibroblast activation and matrix deposition. CONCLUSIONS: Host-microbes interplay potentially determines remodeling activities in the transplanted lung, highlighting new therapeutic opportunities to ultimately improve long-term lung transplant outcome.

[COPD and phenotypes]. / Les phénotypes de la BPCO.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of chronic respiratory diseases which phenotyping is less codified as for asthma yet as essential. The phenotype helps to better understand the evolution of the disease, punctuated by exacerbations and favors a better targeting for treatments and clinical work-up. The latest studies, mostly based on the ECLIPSE and SPIROMICS cohorts, highlight the importance of the search for eosinophilia and the complete assessment of cardiovascular comorbidities. This article will discuss the role of lung function, exacerbations, biomarkers, and comorbidities in COPD phenotyping.

La bronchopneumopathie chronique obstructive (BPCO) représente un groupe hétérogène de patients atteints d'une maladie respiratoire chronique dont le phénotypage est moins codifié mais autant essentiel que celui de l'asthme. Il permet de mieux comprendre l'évolution de la maladie rythmée par des exacerbations, de mieux cibler les traitements et les examens complémentaires. Les dernières études se basant sur les cohortes ECLIPSE et SPIROMICS soulignent l'importance de la recherche d'une éosinophilie et le bilan complet des comorbidités cardiovasculaires. Cet article aborde le rôle des épreuves fonctionnelles respiratoires, des exacerbations, des biomarqueurs et des comorbidités pour le phénotypage de la BPCO.

Development and validation of a simple tool for the assessment of home noninvasive ventilation: the S3-NIV questionnaire.

Patient-centred outcomes are significantly modified by long-term home noninvasive ventilation (NIV), but a short, self-administered, specific tool for routine clinical assessment is lacking. The aim of this study was to develop and validate the S3-NIV questionnaire, a short questionnaire to measure respiratory symptoms, sleep quality and NIV-related side effects.Patients with stable disease who were under long-term home NIV were recruited from three outpatient NIV services. Questionnaire development consisted of a selection of core items for analysis, followed by item reduction, validation and test-retest reliability.338 patients completed a 22-item questionnaire. 11 items were removed because of non-scalability (n=2), redundancy (n=8) and lack of fit (n=1). The final version of the S3-NIV questionnaire consisted of 11 items covering two dimensions: "respiratory symptoms" (Cronbach's α=0.84) and "sleep & NIV-related side effects" (Cronbach's α=0.77). Convergent validity was high between the "respiratory symptoms" subscale of the S3-NIV questionnaire and the St George's Respiratory Questionnaire (rho= -0.76, p<0.001), and between the "sleep & NIV-related side effects" subscale and the Quebec Sleep Questionnaire (rho=0.51, p<0.001). The S3-NIV questionnaire had good test--retest reliability after 4 weeks (intraclass correlation coefficient=0.72).The S3-NIV questionnaire is a short, valid and repeatable self-completed tool for the routine clinical assessment of patients undergoing home NIV.

[COPD and cognitive impairment]. / BPCO et troubles cognitifs.

Patients with chronic respiratory failure, especially COPD, suffer from a multi-systemic disease with organic, behavioral and social consequences that impact largely beyond the respiratory system. Cognitive impairment is associated with decreased quality of life and increased mortality in the general population, but remains underestimated and poorly studied in chronic respiratory diseases despite their increased prevalence. However, there is growing interest in research on the association between cognitive impairment and chronic respiratory diseases. Different risk factors, some modifiable, could contribute to the early development of cognitive disorders in this population. Patients with cognitive impairment need appropriate care to promote adherence to the therapeutic project. Respiratory rehabilitation, as a multimodal intervention, seems to have a positive effect on cognitive functions.

Les sujets insuffisants respiratoires chroniques, surtout ceux atteints d'une BPCO, souffrent d'une maladie multisystémique avec des conséquences biopsychosociales qui dépassent largement le système respiratoire. Les troubles cognitifs sont associés à une diminution de la qualité de vie et à une mortalité accrue dans la population générale, mais ils demeurent sous-estimés dans les maladies respiratoires chroniques malgré leur prévalence augmentée. Différents facteurs, certains modifiables, pourraient contribuer au développement précoce de troubles cognitifs dans cette population qui ne fait pas l'objet d'un dépistage systématique. Les patients avec troubles cognitifs ont besoin de soins adaptés pour favoriser l'adhésion au projet thérapeutique. La réhabilitation respiratoire semble avoir un effet positif sur les fonctions cognitives.

[Pulmonary rehabilitation in respiratory disorders other than COPD : an individualized approach]. / Réhabilitation pulmonaire lors de pathologies autres que la BPCO : un programme sur mesure.

Pulmonary rehabilitation is a multimodal intervention which includes an individualized physical training program, patient education, nutritional assessment and counseling, and recommendations for behavioral changes (smoking cessation, physical activity, nutrition...). This approach, validated and widely accepted by international expert societies in COPD, has been explored and evaluated in other chronic respiratory disorders. This overview analyses the impact of pulmonary rehabilitation in interstitial lung diseases, pulmonary hypertension, lung cancer (pre and post surgery), and morbid obesity. The recent medical literature encourages clinicians to consider the possibility of pulmonary rehabilitation in most chronic pulmonary disorders.

La réhabilitation respiratoire est une intervention multimodale comprenant un entraînement physique personnalisé, un enseignement thérapeutique, une prise en charge nutritionnelle, et un encouragement à des modifications comportementales. Cette approche, validée et recommandée par les sociétés savantes lors de BPCO, est de plus en plus étudiée dans d'autres pathologies pulmonaires chroniques. Ce travail analyse l'impact de la réhabilitation respiratoire lors de pneumopathies interstitielles, d'hypertension pulmonaire, d'obésité morbide et lors de cancer pulmonaire (en phase pré ou postopératoire). Les données les plus récentes encouragent les cliniciens à envisager systématiquement la possibilité d'une réhabilitation respiratoire lors de pathologies respiratoires chroniques.

[Transbronchial cryobiopsies : a minimally invasive tool for the diagnosis of interstitial lung disease]. / Cryobiopsies transbronchiques : diagnostic minimalement invasif de la fibrose pulmonaire.

The diagnosis of interstitial lung disease (ILD) is challenging and relies on a multidisciplinary discussion involving clinical, radiological and sometimes histological features. Bronchoscopic lung cryobiopsies have emerged as a new minimally invasive method of lung sampling and an alternative to surgical lung biopsies. A good diagnostic performance and excellent safety profile make it an interesting and worthful procedure which could decrease the number of patients without proper diagnosis and treatment. There is a need for further studies to standardize the technique in expert centers and to establish its role in the diagnostic work-up of ILD.

Le diagnostic des pneumopathies interstitielles (PI) est complexe et repose sur l'analyse d'éléments cliniques, radiologiques et parfois histologiques dans le cadre d'une discussion multidisciplinaire. Pour l'obtention de biopsies pulmonaires, les cryobiopsies transbronchiques constituent une nouvelle méthode minimalement invasive, alternative aux biopsies chirurgicales. Leur très bonne performance diagnostique et leur profil de sécurité favorable expliquent l'intérêt grandissant pour cette technique qui pourrait permettre de diminuer le nombre de patients n'ayant pas de diagnostic définitif établi et de traitement adapté. Des études restent encore nécessaires, au sein de centres experts, afin de standardiser les modalités pratiques de cette technique et de déterminer sa place dans l'algorithme de prise en charge des PI.

Idiopathic Pulmonary Fibrosis in Switzerland: Diagnosis and Treatment.

Idiopathic pulmonary fibrosis (IPF) is a severe progressive and irreversible lung disease. Novel antifibrotic drugs that slow disease progression are now available. However, many issues regarding patient management remain unanswered, such as the choice between available drugs, their use in particular subgroups and clinical situations, time of treatment onset, termination, combination or switch, or nonpharmacologic management. To guide Swiss respiratory physicians in this evolving field still characterized by numerous areas of uncertainty, the Swiss Working Group for interstitial and rare lung diseases of the Swiss Respiratory Society provides a position paper on the diagnosis and treatment of IPF.

Airway Microbiota Determines Innate Cell Inflammatory or Tissue Remodeling Profiles in Lung Transplantation.

RATIONALE: In lung transplant recipients, long-term graft survival relies on the control of inflammation and tissue remodeling to maintain graft functionality and avoid chronic lung allograft dysfunction. Although advances in clinical practice have improved transplant success, the mechanisms by which the balance between inflammation and remodeling is maintained are largely unknown. OBJECTIVES: To assess whether host-microbe interactions in the transplanted lung determine the immunologic tone of the airways, and consequently could impact graft survival. METHODS: Microbiota DNA and host total RNA were isolated from 203 bronchoalveolar lavages obtained from 112 patients post-lung transplantation. Microbiota composition was determined using 16S ribosomal RNA analysis, and expression of a set of genes involved in prototypic macrophage functions was quantified using real-time quantitative polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: We show that the characteristics of the pulmonary microbiota aligned with distinct innate cell gene expression profiles. Although a nonpolarized activation was associated with bacterial communities consisting of a balance between proinflammatory (e.g., Staphylococcus and Pseudomonas) and low stimulatory (e.g., Prevotella and Streptococcus) bacteria, "inflammatory" and "remodeling" profiles were linked to bacterial dysbiosis. Mechanistic assays provided direct evidence that bacterial dysbiosis could lead to inflammatory or remodeling profiles in macrophages, whereas a balanced microbial community maintained homeostasis. CONCLUSIONS: The crosstalk between bacterial communities and innate immune cells potentially determines the function of the transplanted lung offering novel pathways for intervention strategies.

[Living with bronchiectasis]. / Vivre avec des bronchiectasies.

Bronchiectasis is a chronic condition with a prevalence continuously on the rise. Bronchiectasis have a considerable impact on morbidity, healthcare utilization and quality of life. Pulmonary function tests, microbiological variables and exacerbation rate are useful in the initial and follow-up evaluation. Scores that combine those variables with chest CT findings have been established to predict hospitalizations and mortality. Assessment of health-related quality of life cannot rely on physiological variables measurement. Dedicated questionnaires are therefore needed for that purpose.

La prévalence des bronchiectasies ou dilatations des bronches (DDB) ne cesse d'augmenter. Cette maladie respiratoire chronique a une morbidité considérable, aboutit à une importante consommation de ressources de santé et impacte significativement la qualité de vie. Des variables physiologiques, microbiologiques et la fréquence des exacerbations sont utiles dans l'évaluation initiale et le suivi des patients atteints de DDB. Regroupées sous la forme de scores et associées à l'étendue des bronchiectasies au scanner thoracique, ces variables permettent d'anticiper les hospitalisations et de préciser le pronostic vital de ces patients. L'évaluation de leur qualité de vie ne peut pas reposer sur des mesures de paramètres physiologiques, mais requiert des questionnaires spécifiquement développés à cet effet.

[Inhaled antibiotics for the management of non cystic fibrosis bronchiectasis]. / Antibiotiques inhalés dans la prise en charge des bronchiectasies en dehors de la mucoviscidose.

Bronchiectasis is irreversible bronchial dilatation associated with chronic respiratory symptoms. Management is aimed at reducing symptoms and slowing the progression of the disease by interrupting the vicious circle: bronchial infection, inflammation, altered mucociliary clearance, lung destruction. Unlike the literature on inhaled antibiotics in cystic fibrosis, literature data are limited and of low quality for bronchiectasis of other causes. However, new recommendations from the European Respiratory Society propose the conditional use of inhaled antibiotics to prevent repeated infectious exacerbations and to eradicate Pseudomonas aeruginosa colonization.

Les bronchiectasies sont des dilatations irréversibles des bronches associées à une symptomatologie respiratoire chronique. La prise en charge vise à réduire les symptômes et ralentir la progression de la maladie en interrompant le cercle vicieux : infection bronchique, inflammation, clairance mucociliaire altérée, destruction pulmonaire. Contrairement à la littérature concernant les antibiotiques inhalés dans la mucoviscidose, les données de la littérature sont peu nombreuses et de faible qualité en ce qui concerne les bronchiectasies d'autres causes. Toutefois, de nouvelles recommandations de l'European Respiratory Society proposent l'utilisation conditionnelle des antibiotiques inhalés pour prévenir les exacerbations infectieuses à répétition et pour l'éradication d'une nouvelle colonisation par Pseudomonas aeruginosa.