[COPD : a still neglected condition]. / BPCO : une maladie encore négligée.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung disorder with a complex clinical picture. The diagnosis may be difficult at times, as COPD may develop insidiously and remain unnoticed for a long time. Therefore, general practitioners play a central role in early detection of disease. Suspected COPD may be confirmed by further investigations in collaboration with a pulmonologist. The most recent GOLD guideline defines three COPD risk groups (A-B-E) which should guide the personalized treatment concept. General practitioners are crucial for implementing non-pharmacological measures such as smoking cessation, regular exercise, vaccinations, and patient self-management education. However, this also underlines the challenges to implement the GOLD recommendations in daily practice.

La BPCO est une maladie hétérogène avec un tableau clinique complexe. Le diagnostic n'est pas toujours facile à évoquer, car elle peut se développer insidieusement et passer longtemps inaperçue. Les médecins de premier recours (MPR) jouent donc un rôle central dans le diagnostic précoce. La suspicion de BPCO peut être confirmée en collaboration avec un pneumologue par des examens fonctionnels respiratoires avant l'instauration d'un traitement médicamenteux. Les nouvelles recommandations GOLD, publiées en 2022 définissent trois groupes de risques pour la BPCO (A-B-E). Les MPR sont importants pour la mise en œuvre de mesures accompagnant le traitement (arrêt du tabac, activité physique régulière, vaccinations, éducation thérapeutique). Mais cela souligne également les exigences élevées de la mise en œuvre des recommandations GOLD dans la pratique quotidienne.*.

Long-term outcome of patients with combined post- and pre-capillary pulmonary hypertension.

Aims: Pulmonary hypertension (PH) is a complex clinical condition, and left heart disease is the leading cause. Little is known about the epidemiology and prognosis of combined post- and pre-capillary PH (CpcPH). Methods and results: This retrospective analysis of the Swiss PH Registry included incident patients with CpcPH registered from January 2001 to June 2019 at 13 Swiss hospitals. Patient baseline characteristics [age, sex, mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP), pulmonary vascular resistance (PVR), and risk factors, including World Health Organization (WHO)-functional class (FC), 6 min walk distance (6MWD), and N-terminal pro-brain natriuretic peptide (NT-proBNP), treatment, days of follow-up, and events (death or loss to follow-up) at last visit] were analysed by Kaplan-Meier and Cox regression analyses. Two hundred and thirty-one patients (59.3% women, age 65 ± 12 years, mPAP 48 ± 11 mmHg, PAWP 21 ± 5 mmHg, PVR 7.2 ± 4.8 WU) were included. Survival analyses showed a significantly longer survival for women [hazard ratio (HR) 0.58 (0.38-0.89); P = 0.01] and a higher mortality risk for mPAP > 46 mmHg [HR 1.58 (1.03-2.43); P = 0.04] but no association with age or PVR. Patients stratified to high risk according to four-strata risk assessment had an increased mortality risk compared with patients stratified to low-intermediate risk [HR 2.44 (1.23-4.84); P = 0.01]. A total of 46.8% of CpcPH patients received PH-targeted pharmacotherapy; however, PH-targeted medication was not associated with longer survival. Conclusion: Among patients with CpcPH, women and patients with an mPAP ≤46 mmHg survived longer. Furthermore, risk stratification by using non-invasively assessed risk factors, such as WHO-FC, 6MWD, and NT-proBNP, as proposed for pulmonary arterial hypertension, stratified survival in CpcPH, and might be helpful in the management of these patients.

Using patient-reported outcome measures to assess the effectiveness of social media networking programs for people living with overweight and obesity to adopt a healthier lifestyle.

Introduction: Overweight, obesity, and their associated health complications have become a major public health issue. Online approaches have been rarely attempted to address the problem. The aim of this study was to evaluate the effectiveness of using social media networking for people living with overweight and obesity to adopt a healthier lifestyle with a three-month multidisciplinary healthcare program. Effectiveness was assessed through questionnaires on patient-related outcome measures (PROMs). Materials and methods: Two non-profit associations designed the program delivered to people living with overweight and obesity in a closed group via Facebook, the popular social network. The three-month program had three main axes, namely nutrition, psychology, and physical activity. Anthropomorphic data and sociodemographic profiles were collected. Quality of life (QoL) was assessed at the beginning and at the end of the intervention using PROM questionnaires for six different domains, i.e., body image, eating behavior, physical, sexual, social, and psychological functioning. Results: Six hundred and twenty persons participated in the program; 567 persons consented for the study, and 145 completed the questionnaires entirely. QoL was significantly improved in five out of six domains, i.e., body image, eating behavior, as well as physical, sexual, and psychological functioning. The improvement was valid regardless of age, gender, initial body mass index, person with or without children, educational level (primary versus secondary versus high school), and occupation (employment compared to unemployment or any kind of social assistance). In multivariate analysis, living as a couple was an independent factor correlated to a positive progression in four domains, i.e., body image, eating behavior, as well as physical, and psychological functioning. Conclusion: This study showed that an online lifestyle intervention might be a promising way of improving the quality of life of people living with overweight or obesity.

[COPD - An Underestimated Disease]. / COPD ­ eine unterschätzte Erkrankung.

COPD - An Underestimated Disease Abstract: Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition with a complex clinical picture. The diagnosis is not easy to make because COPD can develop insidiously and remain unnoticed for a long time. Therefore, general practitioners play a central role in the early detection of the disease. Suspected COPD can be confirmed by special examinations in collaboration with pulmonologists. The new GOLD guideline defines three COPD risk groups (A-B-E) which should guide the personalized treatment concept. A short- or long-acting bronchodilator (SAMA/SABA or LAMA/LABA) is recommended for group A, and a dual long-acting bronchodilator therapy (LABA+LAMA) is recommended for group B and E. In case of blood eosinophilia (≥300 cells/µl) and/or recent hospitalization for COPD exacerbation, triple therapy (LABA+LAMA+ICS) is recommended. General practitioners are important in implementing non-pharmacological measures (smoking cessation, regular exercise, vaccinations, patient selfmanagement education). However, this also underlines the high demands of the implementation of the GOLD guideline in daily practice.

The Influence of Methods for Cardiac Output Determination on the Diagnosis of Precapillary Pulmonary Hypertension: A Mathematical Model.

Background: precapillary pulmonary hypertension (PH, PcPH) is now defined as a mean pulmonary artery pressure (mPAP) > 20 mmHg, a pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg and a pulmonary vascular resistance (PVR) > 2 WU. For PVR calculation, the measurement of cardiac output (CO) is necessary. It is generally measured using thermodilution. However, recent data showed that the agreement with direct Fick method, historically the gold standard, is less than previously reported. We aimed to create a mathematical model that calculated the probability of being classified differently (PcPH or unclassified PH) if CO measured by direct Fick was used instead of thermodilution for any individual patients with a mPAP > 20 mmHg and a PAWP ≤ 15 mmHg. Methods: The model is based on Bland and Altman analysis with a normally distributed difference of cardiac output, fixed 1.96 standard deviation of bias, bias and physiological cardiac output limits. Results: Following a literature review of the studies comparing CO measured with direct Fick and thermodilution, we fixed the 1.96 standard deviation of bias at 2 L/min, bias at 0 L/min and physiological resting CO limits between 1.3 L/min and 10.2 L/min. Conclusions: This model can help the clinician to evaluate the potential benefit of measuring CO using direct Fick during the diagnostic work-up and its utility in confirming or ruling out a diagnosis of PcPH in any given patient with a mPAP > 20 mmHg and a PAWP ≤ 15 mmHg.

Disease characteristics and clinical outcome over two decades from the Swiss pulmonary hypertension registry.

Pulmonary hypertension (PH), especially pulmonary arterial and chronic thromboembolic pulmonary hypertension (PAH/CTEPH), are rare and progressive conditions. Despite recent advances in treatment and prognosis, PH is still associated with impaired quality of life and survival. Long-term PH-registry data provide information on the changing PH-epidemiology and may help to direct resources to patient's needs. This retrospective analysis of the Swiss Pulmonary Hypertension Registry includes patients newly diagnosed with PH (mainly PAH/CTEPH) registered from January 2001 to June 2019 at 13 Swiss hospitals. Patient characteristics (age, body mass index, gender, diagnosis), hemodynamics at baseline, treatment, days of follow-up, and events (death, transplantation, pulmonary endarterectomy, or loss to follow-up) at last visit were analyzed. Patients were stratified into four time periods according to their date of diagnosis. Survival was analyzed overall and separately for PAH/CTEPH and time periods. 1427 PH patients were included (thereof 560 PAH, 383 CTEPH). Over the years, age at baseline (mean ± SD) significantly increased from 59 ± 14 years in 2001-2005 to 66 ± 14 years in 2016-2019 (p < 0.001) while the gender distribution tended toward equality. Mean pulmonary artery pressure and pulmonary vascular resistance significantly decreased over time (from 46 ± 15 to 41 ± 11 mmHg, respectively, 9 ± 5 to 7 ± 4 WU, p < 0.001). Three-year survival substantially increased over consecutive periods from 69% to 91% (for PAH 63%-95%, for CTEPH 86%-93%) and was poorer in PAH than CTEPH independently of time period (p < 0.001). Most patients were treated with mono- or combination therapy and an increasing number of CTEPH underwent pulmonary endarterectomy (40% 2016-2019 vs. 15% 2001-2005). This long-term PH registry reveals that over two decades of observation, newly diagnosed patients are older, less predominantly female, have less impaired hemodynamics and a better survival.

Role of Non-Invasive Respiratory Supports in COVID-19 Acute Respiratory Failure Patients with Do Not Intubate Orders.

The current gold-standard treatment for COVID-19-related hypoxemic respiratory failure is invasive mechanical ventilation. However, do not intubate orders (DNI), prevent the use of this treatment in some cases. The aim of this study was to evaluate if non-invasive ventilatory supports can provide a good therapeutic alternative to invasive ventilation in patients with severe COVID-19 infection and a DNI. Data were collected from four centres in three European countries. Patients with severe COVID-19 infection were included. We emulated a hypothetical target trial in which outcomes were compared in patients with a DNI order treated exclusively by non-invasive respiratory support with patients who could be intubated if necessary. We set up a propensity score and an inverse probability of treatment weighting to remove confounding by indication. Four-hundred patients were included: 270 were eligible for intubation and 130 had a DNI order. The adjusted risk ratio for death among patients eligible for intubation was 0.81 (95% CI 0.46 to 1.42). The median length of stay in acute care for survivors was similar between groups (18 (10-31) vs. (19 (13-23.5); p = 0.76). The use of non-invasive respiratory support is a good compromise for patients with severe COVID-19 and a do not intubate order.

[Place of the respiratory physiotherapist in the Covid-19 crisis: Neuchâtel experience]. / Place du physiothérapeute respiratoire dans la crise Covid-19 : expérience neuchâteloise.

The physiotherapy service became an important player in the care of patients with COVID-19 at Pourtalès hospital (Neuchâtel, Switzerland), illustrating its important role in the organization of acute care units. The workforce was increased, and the diaries extended (7/7d, 24/24h). Respiratory physiotherapists were largely involved in the initiation and the adaptation of the respiratory therapy in the units dedicated to Covid-19 patients (emergency, intensive care and pulmonology units), such as oxygen therapy and both invasive and non-invasive ventilation. Rehabilitation was also early initiated in order to limit the risk of intensive care unit-acquired polyneuromyopathy and to prevent physical deconditioning.

Le Service de physiothérapie s'est inscrit comme un acteur important dans la prise en charge des patients Covid-19 à l'Hôpital Pourtalès (Neuchâtel, Suisse), illustrant son rôle important dans l'organigramme des unités de soins aigus. L'effectif a été augmenté et les horaires étendus (7 j/7, 24 h/24). Les physiothérapeutes spécialisés dans le domaine respiratoire ont activement participé à la mise en route des traitements respiratoires et à leur adaptation dans les unités dédiées aux patients Covid-19 (urgences, soins intensifs et pneumologie), tels que l'oxygénothérapie et l'assistance ventilatoire invasive et non invasive. Une réhabilitation a par ailleurs été initiée précocement afin de limiter le risque de polyneuromyopathie acquise aux soins intensifs et de prévenir le déconditionnement physique.

[Hyperventilation syndrome and dysfunctional breathing†: update]. / Syndrome d'hyperventilation et respiration dysfonctionnelle†: mise à jour.

Dysfunctional breathing is a group of respiratory disorders that cause dyspnea, with no organic cause, or that are disproportionate to the organ involvement. Hyperventilation syndrome is the best-known manifestation of dysfunctional breathing. It is very often associated or secondary to anxiety disorders. When the diagnosis of dysfunctional breathing is not considered, it can lead to multiple and unnecessary investigations, further increasing anxiety. The diagnosis is based on various tests, none of which is really specific, and remains based on a bundle of arguments. Management must be adapted for each patient and is based on respiratory rehabilitation techniques.

La respiration dysfonctionnelle représente un groupe de troubles respiratoires entraînant une dyspnée sans cause organique, ou disproportionnée par rapport à l'atteinte d'organe. Le syndrome d'hyperventilation en est la manifestation la plus connue. Il est très souvent associé ou secondaire à des troubles anxieux. Lorsque le diagnostic de respiration dysfonctionnelle n'est pas envisagé, cela peut conduire à des investigations multiples et inutiles, augmentant encore l'anxiété du patient. Il repose sur différents tests, dont aucun n'est vraiment spécifique, et reste basé sur un faisceau d'arguments. La prise en charge doit être adaptée pour chaque patient et nécessite des techniques de rééducation respiratoire.

[Allergic bronchopulmonary aspergillosis]. / Aspergillose bronchopulmonaire allergique.

Allergic bronchopulmonary aspergillosis (ABPA) is a specific complex immunological response to the spores of Aspergillus fumigatus (Af) colonizing the bronchi of asthmatic or cystic fibrosis patients. Recurrent episodes of bronchial obstruction and inflammation, as well as mucoid impaction cause bronchiectasis, pulmonary infiltrates and fibrotic alterations of the lung parenchyma, resulting in significant morbidity and mortality. The pathogenesis of ABPA remains incompletely understood, so it is not clear why certain colonized subjects develop hypersensitivity to Af, and why some sensitized patients develop ABPA and others do not. There is no simple and specific test for diagnosing ABPA. The diagnosis is based on the combination of clinical, radiological and immunological criteria. Systemic steroids are the cornerstone of treatment.

L'aspergillose bronchopulmonaire allergique (ABPA) est une réponse immunologique spécifique complexe contre les spores d'Aspergillus fumigatus (Af) qui colonisent les bronches de patients asthmatiques ou mucoviscidosiques. Les épisodes répétés d'obstruction et d'inflammation bronchiques et d'impactions mucoïdes génèrent des bronchiectasies, des infiltrats pulmonaires et des altérations fibrotiques du parenchyme pulmonaire, d'où une morbi-mortalité significative. La pathogenèse de l'ABPA reste mal comprise, si bien qu'on ne sait pas véritablement pourquoi certains sujets colonisés développent une hypersensibilité à Af, et pourquoi certains patients sensibilisés développent une ABPA et d'autres pas. Il n'y a pas de test simple et spécifique qui permette de diagnostiquer une ABPA. Le diagnostic se base sur l'association de critères cliniques, radiologiques et immunologiques. Les stéroïdes systémiques sont la pierre angulaire du traitement.

[Antifibrotic therapy and progressive lung fibrosis]. / Traitement antifibrotique et fibrose pulmonaire progressive.

A significant proportion - up to 40 % - of patients suffering from fibrosing interstitial pneumonia will acquire a progressive phenotype which shares genetic and pathogenic mechanisms, as well a clinical behavior similar to those of idiopathic pulmonary fibrosis (IPF). It therefore makes sense to suggest that molecules with antifibrotic properties such as pirfenidone and nintedanib could be effective in patients with progressive fibrosing interstitial lung disease as they are in patients with IPF. The first studies published on this topic show encouraging results which however have to be confirmed on a larger scale.

Un pourcentage important ­ jusqu'à 40 % ­ de patients qui présentent une pneumopathie interstitielle fibrosante va acquérir un phénotype progressif qui partage, avec la fibrose pulmonaire idiopathique (FPI), des mécanismes génétiques et pathogéniques ainsi qu'un comportement clinique relativement similaires. Il est donc logique de penser que des molécules dotées de propriétés antifibrotiques comme la pirfénidone et le nintédanib pourraient être efficaces chez les patients avec pneumopathie interstitielle fibrosante progressive comme elles le sont chez ceux avec FPI. Les premières études publiées sur le sujet montrent des résultats encourageants qui doivent toutefois être confirmés à plus large échelle.

Endobronchial coil therapy in severe emphysema: 6-month outcomes from a Swiss National Registry.

BACKGROUND: Endobronchial coils have been demonstrated in three randomized, controlled trials to improve quality of life, exercise tolerance, and lung function in patients with severe emphysema. This therapy is CE-marked and commercially available in Switzerland. Coil treated patients are followed in a post-market Swiss registry to collect safety and effectiveness data in routine clinical practice. METHODS: The Swiss coil registry was initiated in October 2013. At the end of November 2016, an interim analysis of all 64 patients treated in five centers was performed to evaluate safety and effectiveness at six months post treatment. RESULTS: patients had completed bilateral treatment with 6-month follow up at the time of data analysis. Patients had very severe, symptomatic emphysema and hyperinflation [38% male, mean age 66 years, BMI 24, FEV1 30% pred., residual volume (RV) 247% pred., 6-minute walking distance (6-MWD) 272 m, St. George Respiratory Questionnaire (SGRQ) 57 points]. Up to 6 months following treatment, seven serious adverse events (SAE) were reported in 6/29 patients. No device removals were necessary. At 6 months, responder rates [% achieving the minimal clinically important difference (MCID)] were as follows: RV (-0.35 L) 76%; FEV1 (+10%) 57%; SGRQ (-4 points) 87%; 6MWD (+26 m) 60%. CONCLUSIONS: Endobronchial coil therapy performed in expert centers in Switzerland yields high 6-month responder rates across all relevant outcome.

Quantifying patient centered outcomes associated with the use of bilateral endobronchial coil treatment in patients with severe emphysema.

OBJECTIVE: To determine the impact of endobronchial coils on health-related quality-of-life (HRQoL). This paper utilizes trial data to identify the predictors of HRQoL in patients with severe emphysema, and subsequently estimates the impact of a new treatment on HRQoL (measured by utilities). These utility estimates are used to generate indicative long-term QALY estimates for a range of clinically plausible scenarios as a precursor to cost-effectiveness analyses. METHODS: Patient level HRQoL data from RENEW and the National Emphysema Treatment Trial (NETT) were combined and mapped to generic EuroQol 5-dimension health utility questionnaire (EQ-5D) values using a published algorithm. Multilevel statistical models were developed using treatment, time, response, and baseline characteristics (EQ-5D, age, gender, FEV1, lung RV) to predict EQ-5D over time. Lifetime QALY estimates were generated using published survival data from NETT (assuming no impact of treatment on mortality) and four clinically plausible response profiles. Each response profile was combined with assumptions around treatment impact (constant or time varying). RESULTS: After controlling for baseline characteristics, both treatment and response had a statistically significant impact (p < .001) on utility (+0.101 and +0.061, respectively). When combined with selected baseline characteristics and time, Coils and Standard of Care (SoC) generated more QALYs than SoC alone in all scenarios, with incremental lifetime benefit ranging from 0.29-0.55 QALYs. CONCLUSIONS: Coils and SoC resulted in statistically significant improvements in HRQoL compared to SoC alone in patients with severe emphysema.

Multicentre observational screening survey for the detection of CTEPH following pulmonary embolism.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe complication of pulmonary embolism. Its incidence following pulmonary embolism is debated. Active screening for CTEPH in patients with acute pulmonary embolism is yet to be recommended.This prospective, multicentre, observational study (Multicentre Observational Screening Survey for the Detection of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Following Pulmonary Embolism (INPUT on PE); ISRCTN61417303) included patients with acute pulmonary embolism from 11 centres in Switzerland from March 2009 to November 2016. Screening for possible CTEPH was performed at 6, 12 and 24 months using a stepwise algorithm that included a dyspnoea phone-based survey, transthoracic echocardiography, right heart catheterisation and radiological confirmation of CTEPH.Out of 1699 patients with pulmonary embolism, 508 patients were assessed for CTEPH screening over 2 years. CTEPH incidence following pulmonary embolism was 3.7 per 1000 patient-years, with a 2-year cumulative incidence of 0.79%. The Swiss pulmonary hypertension registry consulted in December 2016 did not report additional CTEPH cases in these patients. The survey yielded 100% sensitivity and 81.6% specificity. The second step echocardiography in newly dyspnoeic patients showed a negative predictive value of 100%.CTEPH is a rare but treatable disease. A simple and sensitive way for CTEPH screening in patients with acute pulmonary embolism is recommended.

Identification of Antigenic Proteins from Lichtheimia corymbifera for Farmer's Lung Disease Diagnosis.

The use of recombinant antigens has been shown to improve both the sensitivity and the standardization of the serological diagnosis of Farmer's lung disease (FLD). The aim of this study was to complete the panel of recombinant antigens available for FLD serodiagnosis with antigens of Lichtheimia corymbifera, known to be involved in FLD. L. corymbifera proteins were thus separated by 2D electrophoresis and subjected to western blotting with sera from 7 patients with FLD and 9 healthy exposed controls (HEC). FLD-associated immunoreactive proteins were identified by mass spectrometry based on a protein database specifically created for this study and subsequently produced as recombinant antigens. The ability of recombinant antigens to discriminate patients with FLD from controls was assessed by ELISA performed with sera from FLD patients (n = 41) and controls (n = 43) recruited from five university hospital pneumology departments of France and Switzerland. Forty-one FLD-associated immunoreactive proteins from L. corymbifera were identified. Six of them were produced as recombinant antigens. With a sensitivity and specificity of 81.4 and 77.3% respectively, dihydrolipoyl dehydrogenase was the most effective antigen for discriminating FLD patients from HEC. ELISA performed with the putative proteasome subunit alpha type as an antigen was especially specific (88.6%) and could thus be used for FLD confirmation. The production of recombinant antigens from L. corymbifera represents an additional step towards the development of a standardized ELISA kit for FLD diagnosis.

Long-term data from the Swiss pulmonary hypertension registry.

BACKGROUND: Registries are important for real-life epidemiology on different pulmonary hypertension (PH) groups. OBJECTIVE: To provide long-term data of the Swiss PH registry of 1998-2012. METHODS: PH patients have been classified into 5 groups and registered upon written informed consent at 5 university and 8 associated hospitals since 1998. New York Heart Association (NYHA) class, 6-min walk distance, hemodynamics and therapy were registered at baseline. Patients were regularly followed, and therapy and events (death, transplantation, endarterectomy or loss to follow-up) registered. The data were stratified according to the time of diagnosis into prevalent before 2000 and incident during 2000-2004, 2005-2008 and 2009-2012. RESULTS: From 996 (53% female) PH patients, 549 had pulmonary arterial hypertension (PAH), 36 PH due to left heart disease, 127 due to lung disease, 249 to chronic thromboembolic PH (CTEPH) and 35 to miscellaneous PH. Age and BMI significantly increased over time, whereas hemodynamic severity decreased. Overall, event-free survival was 84, 72, 64 and 58% for the years 1-4 and similar for time periods since 2000, but better during the more recent periods for PAH and CTEPH. Of all PAH cases, 89% had target medical therapy and 43% combination therapy. Of CTEPH patients, 14 and 2% underwent pulmonary endarterectomy or transplantation, respectively; 87% were treated with PAH target therapy. CONCLUSION: Since 2000, the incident Swiss PH patients registered were older, hemodynamically better and mostly treated with PAH target therapies. Survival has been better for PAH and CTEPH diagnosed since 2008 compared with earlier diagnosis or other classifications.

Western blotting as a tool for the serodiagnosis of farmer's lung disease: validation with Lichtheimia corymbifera protein extracts.

Electrosyneresis and double diffusion are immunoprecipitation techniques commonly used in the serological diagnosis of Farmer's lung disease (FLD). These techniques are reliable but lack standardization. The aim of this study was to evaluate Western blotting for the serodiagnosis of FLD. We carried out Western blotting with an antigenic extract of Lichtheimia corymbifera, an important aetiological agent of the disease. The membranes were probed with sera from 21 patients with FLD and 21 healthy exposed controls to examine the IgG antibody responses against purified somatic antigens. Given the low prevalence of the disease, 21 patients could be considered as a relevant series. Four bands were significantly more frequently represented in membranes probed with FLD sera (bands at 27.7, 40.5, 44.0 and 50.5 kDa) than those probed with control sera. We assessed the diagnostic value of different criteria alone or in combination. The diagnostic accuracy of the test was highest with the inclusion of at least two of the following criteria: at least five bands on the strip and the presence of one band at 40.5 or 44.0 kDa. Sensitivity, specificity and positive and negative predictive values were all 81%, and the odds ratio was 18.06. Inclusion of bands of high intensity diminished rather than improved the diagnostic value of the test. We concluded that Western blotting is a valuable technique for the serodiagnosis of FLD. The industrial production of ready-to-use membranes would enable the routine use of this technique in laboratories, and provide reliable and standardized diagnostic results within a few hours.

Immunoreactive proteins of Saccharopolyspora rectivirgula for farmer's lung serodiagnosis.

PURPOSE: Saccharopolyspora rectivirgula is the principal cause of farmer's lung disease (FLD). Serodiagnosis is based on immunoprecipitation techniques or enzyme immunoassays with homemade crude antigens and is not standardized. We aimed to produce specific recombinant antigens for the development of a standardized ELISA. EXPERIMENTAL DESIGN: We recruited 41 patients and 43 healthy exposed controls from five university hospital pneumology departments in France and Switzerland. S. rectivirgula proteins were extracted, separated by 2D electrophoresis, and subjected to Western blotting, with sera from FLD patients or controls. FLD-specific proteins were identified by MS and were produced as recombinant antigens. The diagnostic performance of ELISA tests using the recombinant antigens was assessed with all the sera from FLD patients and controls. RESULTS: We identified 25 FLD-specific proteins, some of which play important roles in transport, nutrition, or virulence. We produced 17 of these proteins as recombinant antigens and assessed their suitability for inclusion in the ELISA test. A combination of three of these proteins (SR1FA, SR17, and SR22) proved remarkably effective at discriminating between patients and controls, with a sensitivity of 83% and a specificity of 77%. CONCLUSIONS AND CLINICAL RELEVANCE: The recombinant antigens produced in this study constitute a major step toward the improvement of diagnostic performance and the standardization of FLD serodiagnosis.