Rituximab and mycophenolate mofetil combination in patients with interstitial lung disease (EVER-ILD): a double-blind, randomised, placebo-controlled trial.

BACKGROUND: Standard of care for interstitial lung disease (ILD) with a nonspecific interstitial pneumonia (NSIP) pattern proposes mycophenolate mofetil (MMF) as one of the first-step therapies while rituximab is used as rescue therapy. METHODS: In a randomised, double-blind, two-parallel group, placebo-controlled trial (NCT02990286), patients with connective tissue disease-associated ILD or idiopathic interstitial pneumonia (with or without autoimmune features) and a NSIP pattern (defined on NSIP pathological pattern or on integration of clinicobiological data and a NSIP-like high-resolution computed tomography pattern) were randomly assigned in a 1:1 ratio to receive rituximab (1000 mg) or placebo on day 1 and day 15 in addition to MMF (2 g daily) for 6 months. The primary end-point was the change in percent predicted forced vital capacity (FVC) from baseline to 6 months analysed by a linear mixed model for repeated measures analysis. Secondary end-points included progression-free survival (PFS) up to 6 months and safety. FINDINGS: Between January 2017 and January 2019, 122 randomised patients received at least one dose of rituximab (n=63) or placebo (n=59). The least-squares mean change from baseline to 6 months in FVC (% predicted) was +1.60 (se 1.13) in the rituximab+MMF group and -2.01 (se 1.17) in the placebo+MMF group (between-group difference 3.60, 95% CI 0.41-6.80; p=0.0273). PFS was better in the rituximab+MMF group (crude hazard ratio 0.47, 95% CI 0.23-0.96; p=0.03). Serious adverse events occurred in 26 (41%) patients of the rituximab+MMF group and in 23 (39%) of the placebo+MMF group. Nine infections were reported in the rituximab+MMF group (five bacterial infections, three viral infections, one other) and four bacterial infections in the placebo+MMF group. INTERPRETATION: Combination of rituximab and MMF was superior to MMF alone in patients with ILD and a NSIP pattern. The use of this combination must take into consideration the risk of viral infection.

French recommendations for the diagnosis and management of lymphangioleiomyomatosis.

BACKGROUND: The present article is an English-language version of the French National Diagnostic and Care Protocol, a pragmatic tool to optimize and harmonize the diagnosis, care pathway, management and follow-up of lymphangioleiomyomatosis in France. METHODS: Practical recommendations were developed in accordance with the method for developing a National Diagnosis and Care Protocol for rare diseases of the Haute Autorité de Santé and following international guidelines and literature on lymphangioleiomyomatosis. It was developed by a multidisciplinary group, with the help of patient representatives and of RespiFIL, the rare disease network on respiratory diseases. RESULTS: Lymphangioleiomyomatosis is a rare lung disease characterised by a proliferation of smooth muscle cells that leads to the formation of multiple lung cysts. It occurs sporadically or as part of a genetic disease called tuberous sclerosis complex (TSC). The document addresses multiple aspects of the disease, to guide the clinicians regarding when to suspect a diagnosis of lymphangioleiomyomatosis, what to do in case of recurrent pneumothorax or angiomyolipomas, what investigations are needed to make the diagnosis of lymphangioleiomyomatosis, what the diagnostic criteria are for lymphangioleiomyomatosis, what the principles of management are, and how follow-up can be organised. Recommendations are made regarding the use of pharmaceutical specialties and treatment other than medications. CONCLUSION: These recommendations are intended to guide the diagnosis and practical management of pulmonary lymphangioleiomyomatosis.

The effect of a pressure ventilatory support on quadriceps endurance is maintained after exercise training in severe COPD patients. A longitudinal randomized, cross over study.

Purpose: In severe chronic obstructive pulmonary disease (COPD) patients, the application of an inspiratory pressure support (IPS) during exercise increases exercise tolerance and the benefit of exercise training during pulmonary rehabilitation (PR). Moreover, it improves quadriceps endurance after a session of cycling exercise suggesting a reduced muscle fatigue. We looked for the persistence of this effect after PR and sought an association between the improved quadriceps endurance with IPS and the training load during PR. Patients and methods: We studied 20 patients with severe COPD (6 in stage 3and 14 in stage 4 of GOLD) before and after PR. As part of a PR program, patients completed 16 cycling sessions over 6 weeks with the addition of IPS during exercise. As a surrogate of muscular fatigue, quadriceps endurance was measured at 70% of maximal strength in a control condition, after a constant work rate exercise test (CWR) with IPS (TlimQ IPS) or with a sham ventilation (TlimQsham), in a random order. These tests were repeated similarly at the end of PR. Results: PR was associated with a significant increase in maximal power output, cycling endurance, quadriceps strength and endurance. Session training load (power output x duration of the session) increased by 142% during the course of the program. Before PR, CWR duration increases with IPS compared to sham ventilation (Δtime = +244s, p = 0.001). Compared to control condition, post-exercise TlimQ reduction was lower with IPS at isotime than at the end of CWR or than with sham ventilation (-9 ± 21%, -18 ± 16% and -23 ± 18%, respectively, p = 0.09, p < 0.0001 and p < 0.0001). After PR, the post-exercise decrease of TlimQ was reduced after IPS compared to sham (-9 ± 18% vs. -21 ± 17%, respectively, p = 0.004). No relationship was found between the prevention of quadriceps fatigue and the training load. Conclusion: In severe COPD patients, the beneficial effect of a ventilator support on quadriceps endurance persisted after PR with IPS. However, it was not related to the increase in training load, and could not predict the training response to non-invasive ventilation during exercise.

Chest ultrasound findings in usual interstitial pneumonia patterns: a pilot study.

It is unknown what role chest ultrasound plays in distinguishing the various usual interstitial pneumonia (UIP) patterns of high-resolution chest tomography (HRCT). The purpose of this study was to see if there was a link between the results of chest ultrasound (u/s) and HRCT in patients with idiopathic pulmonary fibrosis (IPF). We performed chest u/s in 16 patients with UIP and probable UIP patterns to indeterminate UIP and alternative diagnosis patterns in this single center prospective study to determine any possible relationship with the HRCT findings. A chest radiologist reviewed each HRCT to determine the pattern in accordance with the American Thoracic Society (ATS) / European Respiratory Society (ERS) Guidelines. The local multidisciplinary committee validated the patients' diagnoses before they were included. When compared to the indeterminate for UIP or alternative diagnosis pattern group, there was a trend (p=0.07) toward the presence of more B lines in UIP or probable UIP patterns. There was no statistically significant difference in the presence of small, large, white lung, or pleural line thickening >5mm. Subgroup analysis revealed that patients with honeycombing were more likely to have a fragmented pleural line (p=0.04). To summarize, in our pilot study, chest u/s appears unable to differentiate UIP and probable UIP patterns from indeterminate UIP and alternative diagnosis patterns. However, it appears that this technique can be used to recognize the honeycombing pattern.

Did COVID-19 impact Positive Airway Pressure adherence in 2020? A cross-sectional study of 8477 patients with sleep apnea.

BACKGROUND: Whether the COVID-19 pandemic impacts Positive Airway Pressure (PAP) adherence over the long-term is unknown and only preliminary short-term data have been reported. METHODS: With the aim of describing the impact of the first and second waves of COVID-19 on PAP adherence during 2020 in France, we designed a cross-sectional study of Sleep-Apnea (SA)-patients under PAP telemonitoring. To examine PAP adherence in adult SA patients, we assessed de-identified data from a non-profit healthcare provider database during the period January 1, 2019 to December 31, 2020. Included patients met the following criteria: (i) PAP-treated for at least 4 months before January 1, 2019 and with continuous PAP during both 2019 and 2020; (ii) ≥ 360 daily PAP telemonitored data per year. For PAP adherence, data were collected using the PAP-software. RESULTS: 8477/10482 patients were finally included in the analysis [72.4% male, median age 70 years (IQ25-75: 61-77], 25.6% < 62 years old, initial Apnea-Hypopnea Index (AHI) of 41 (31-59)/h. Median PAP adherence was 7.21 (6.12-8.10) h/day in 2020 versus 7.12 (6.05-8.02) h/day in 2019, p < 0.001. The median difference in PAP adherence between the first 2020 lockdown and the corresponding 2019 weeks was 9.75 (CI95% 8.75-10.75) min/day, p < 0.001. The median difference in PAP adherence between the second 2020 lockdown and the corresponding 2019 weeks was 5.00 (CI95% 4.00-6.00) min/day, p < 0.001. If we consider the minimal clinically important difference of 30 min for PAP adherence, 30.4% and 26% of the patients increased their PAP adherence by at least 30 min during the first and second lockdowns respectively; 17.6% and 19.3% of the patients lowered their PAP adherence by at least 30 min in the first and second lockdowns, respectively. CONCLUSION: During the first and second lockdowns, the COVID-19 pandemic had a clinically irrelevant effect on PAP adherence for the study population. Future studies are needed to describe COVID-19 pandemic impact on PAP adherence not only for long-term PAP-treated SA patients but also for incident cases. Trial registration The COVADENE study was registered on March 1st, 2021 on ClinicalTrials.gov (Identifier: NCT04775966).

Insulin Resistance and Type 2 Diabetes in Asymptomatic Obstructive Sleep Apnea: Results of the PROOF Cohort Study After 7 Years of Follow-Up.

The aim of the study was to assess potential associations between obstructive sleep apnea (OSA) and the occurrence of diabetes mellitus and insulin resistance in the elderly. Nondiabetic volunteers (n = 549) with undiagnosed or untreated asymptomatic OSA (66.2+/-1 years at the inclusion) were evaluated as an ancillary study of the PROOF cohort study (n = 1,011). After 7 years follow-up, 494 subjects underwent assessment of fasting insulin and glucose levels. OSA was defined by an apnea-hypopnea index (AHI) of ≥15/h using polygraphy. Diabetes mellitus was defined by a fasting glucose ≥ 1.26 g/L and/or when requiring pharmacological treatment, while insulin resistance corresponded to HOMA-IR ≥ 2. Asymptomatic OSA subjects (men or women) did not display increased risk of incident diabetes (2.8 vs. 3.9%, p = 0.51). However, there was a greater frequency of insulin resistance in subjects with severe OSA (AHI > 30) [OR 2.21; 95% CI (1.22-4.02); p = 0.009]. Furthermore, multiple logistic regression showed that triglycerides levels [OR 1.61; 95% CI (1.10-2.36); p = 0.01] and fasting glycaemia [OR 4.69; 95% CI (1.12-192.78); p = 0.04], but not AHI or oxyhemoglobin desaturation index were independently associated with higher rate of insulin resistance. The deleterious metabolic effect of asymptomatic OSA in the population may be indirectly mediated via perturbations in lipids, and is particularly likely to become manifest in severe apneic subjects with higher glycemic levels.

Sleep disturbances and related disordered breathing after hip replacement surgery: A randomised controlled trial.

INTRODUCTION: Mechanisms of postoperative sleep architecture disturbances and sleep-disordered breathing are uncertain. The authors hypothesised that patients undergoing surgery under regional anaesthesia without opioids used for postoperative analgesia would experience lesser changes in these parameters than patients operated under general anaesthesia with per- and postoperative opioids. PATIENTS AND METHODS: After ethical approval and informed consent, patients undergoing total hip replacement were included in a prospective, randomised trial comparing 3 groups of patients: (1) S-LPB group receiving spinal anaesthesia and postoperative analgesia by lumbar plexus block; (2) GA-PCA group receiving general anaesthesia and postoperative analgesia by morphine patient-controlled analgesia; (3) GA-LPB group receiving general anaesthesia and postoperative analgesia by lumbar plexus block. Outcome measurements were polysomnographic parameters of sleep architecture and sleep-disordered breathing. RESULTS: Eighteen patients completed the 5-night study protocol (preoperative night: N-1, postoperative nights: N1 to N4). The percentage of rapid eye movement (REM) sleep decreased by 49% and 47% during N1 in the GA-PCA and GA-LPB groups respectively. A rebound phenomenon of more than 40% in the GA-PCA group and 25% in the GA-LPB group was observed during N2 and N3. Apnoea hypopnoea index (AHI) and the number of arousals per hour were significantly increased during N2 and N3 when compared with N-1 in the GA-groups. No sleep architecture disturbances and no sleep-disordered breathing were measured in the S-LPB group. CONCLUSION: Postoperative sleep architecture and breathing pattern were disturbed in GA groups. Both were preserved under spinal anaesthesia associated with a free opioid postoperative analgesia.

Burden and Characteristics of Severe Chronic Hypoxemia in a Real-World Cohort of Subjects with COPD.

BACKGROUND: Chronic respiratory failure may occur as a consequence of chronic obstructive pulmonary disease (COPD) and is associated with significant morbidity and mortality. Hypoxemia is determined by underlying disease characteristics and comorbidities. Severe hypoxemia is typically only found in subjects with severe airflow obstruction (FEV1<50% predicted). However, how hypoxemia relates to disease characteristics is not fully understood. METHODS: In the French Initiatives BPCO real-life cohort, arterial blood gases were routinely collected in most patients. Relationships between severe hypoxemia, defined by a Pa02<60 mmHg (8 kPa) and clinical/lung function features, comorbidities and mortality were assessed. In subjects with severe hypoxemia, clinical characteristics and comorbidities were compared between those with non-severe versus severe airflow limitation. Classification and regression trees (CART) were used to define clinically relevant subgroups (phenotypes). RESULTS: Arterial blood gases were available from 887 subjects, of which 146 (16%) exhibited severe hypoxemia. Compared to subjects with a PaO2≥60 mmHg, the severe hypoxemia group exhibited higher mMRC dyspnea score, lower FEV1, higher RV and RV/TLC, more impaired quality of life, lower 6-minute walking distance, less frequent history of asthma, more frequent diabetes and higher 3-year mortality rate (14% versus 8%, p=0.026). Compared to subjects with Pa02<60 mmHg and FEV1<50% (n=115, 13%), those with severe hypoxemia but FEV1≥50% predicted (n=31) were older, had higher BMI, less hyperinflation, better quality of life and a higher rate of diabetes (29% versus 13%, p=0.02). Severe hypoxemia was better related to CART-defined phenotypes than to GOLD ABCD classification. CONCLUSION: In this cohort of stable COPD subjects, severe hypoxemia was associated with worse prognosis and more severe symptoms, airflow limitation and hyperinflation. Compared to subjects with severe hypoxemia and severe airflow limitation, subjects with severe hypoxemia despite non-severe airflow limitation were older, had higher BMI and more diagnosed diabetes. TRIAL REGISTRATION: 04-479.

Quadriceps Endurance Increases Following Cycling Exercise With Non-Invasive Ventilation In Moderate-To-Severe COPD Patients. A Non-Randomized Controlled Study.

Purpose: Application of non-invasive ventilation (NIV) during exercise improves exercise tolerance in severe COPD patients; however, the underlying mechanism is only partially unraveled. As part of its known effect to unload the respiratory muscles, we looked for the influence of NIV on post-exercise quadriceps muscle endurance. Patients and methods: We included 25 severe COPD patients entering an outpatient pulmonary rehabilitation program. They performed, on successive days, three quadriceps endurance tests at 70% of the maximal strength (1RM) to task failure (TlimQ); 1) control condition; 2) following constant load cycling exercise to exhaustion without Inspiratory Pressure Support (TlimQ IPS-); 3) following the same cycling exercise with IPS (TlmQ IPS+). Results: Dyspnea Borg score was significantly reduced at the end of the constant load cycling exercise with IPS+ compared to IPS- (3.5±2.6 to 4.3±2.3, p<0.05). Compared to controlled condition, TlimQ was reduced from 78.9±22.7 s to 64.7±22.1 s (p<0.01) with IPS+ and to 48.9±13.7 s (p<0.001) with IPS-. Sensitive analysis revealed a positive effect of NIV on TlimQ in only 15 of the 25 included patients (60%) and was unpredictable from exercise tolerance or maximal quadriceps strength. Conclusion: Using a simple muscle endurance test, we showed the protective effect of NIV on the exercise-induced quadriceps dysfunction. This beneficial effect is inconstant in our small series of patients and could not be predicted by exercise capacity or endurance to exercise. However, measuring quadriceps muscle endurance following a session of exercise could determine in which patient NIV would improve the benefit of pulmonary rehabilitation.

Relationship between gender and survival in a real-life cohort of patients with COPD.

BACKGROUND: Although COPD affects both men and women, its prevalence is increasing more rapidly in women. Disease outcomes appear different among women with more frequent dyspnea and anxiety or depression but whether this translates into a different prognosis remains to be determined. Our aim was to assess whether the greater clinical impact of COPD in women was associated with differences in 3-year mortality rates. METHODS: In the French Initiatives BPCO real-world cohort, 177 women were matched up to 458 menon age (within 5-year intervals) and FEV1 (within 5% predicted intervals). 3-year mortality rate and survival were analyzed. Univariate and multivariate logistic regression analyses were performed. RESULTS: For a given age and level of airflow obstruction, women with COPD had more severe dyspnea, lower BMI, and were more likely to exhibit anxiety. Nevertheless, three-year mortality rate was comparable among men and women, respectively 11.2 and 10.8%. In a multivariate model, the only factors significantly associated with mortality were dyspnea and malnutrition but not gender. CONCLUSION: Although women with COPD experience higher levels of dyspnea and anxiety than men at comparable levels of age and FEV1, these differences do not translate into variations in 3-year mortality rates. TRIAL REGISTRATION: 04-479.

Predictors in routine practice of 6-min walking distance and oxygen desaturation in patients with COPD: impact of comorbidities.

Background: The 6-min walk test (6MWT) allows exercise tolerance to be assessed, and it has a significant prognostic value in COPD. The goal of this study was to analyse the determinants (obtained in routine practice) of a low 6-min walking distance (6MWD) and exercise-induced desaturation (EID) in COPD, including comorbidities. Methods: Patients were recruited from the real-life French COPD cohort "Initiatives BPCO". A low 6MWD was defined as <350 m. EID was defined by a minimum pulse oxygen saturation (SpO2)<90% and delta SpO2≥4% from baseline. Multivariate logistic regression analyses assessed the influence on 6MWD and EID of age, sex, obesity (body mass index, BMI >30 kg/m2), low BMI (BMI <18.5 kg/m2), modified Medical Research Council (mMRC) dyspnea scale, FEV1% pred, FVC % pred, hyperinflation and comorbidities including cardiovascular diseases. Results: Among 440 patients with available 6MWT data, a 6MWD <350 m was found in 146 patients (33%), which was positively associated in multivariate analyses with age and mMRC and negatively with resting SpO2 and FVC % pred (rescaled r2=0.34), whereas no comorbidity was associated with a low 6WMD. EID was found in 155 patients (35%). This was positively associated with hypertension and negatively with age, obesity, FEV1% pred and resting SpO2 (rescaled r2=0.37). Conclusion: 6MWD and EID exhibit different determinants in COPD with a minor impact of comorbidities limited to hypertension in EID and to obesity, which was unexpectedly associated with less EID. Other variables including age, routine resting lung function and SpO2 were weakly associated with 6MWD and EID. Altogether, these results suggest that 6MWT performance remains difficult to predict with routine clinical/functional parameters.

Phrenic Nerve Conduction in Healthy Subjects.

INTRODUCTION: Assessment of diaphragm compound muscle action potential by noninvasive phrenic nerve stimulation at the neck is well described. However, normal values in a large cohort of healthy subjects are lacking. Our objective was to determine reference values of phrenic nerve conduction in healthy subjects. METHODS: We recruited 155 healthy subjects (25-79 years old) and measured mean amplitude (PhrenAmp) and latency (PhrenLat) of motor responses according to Bolton's method. RESULTS: The lower limit for PhrenAmp was 0.28 and 0.25 mV and the upper limit for PhrenLat was 8.41 and 8.56 ms for right and left side, respectively. PhrenLat was correlated with age. PhrenAmp, PhrenLat and area were significantly higher in men. Tolerance to phrenic nerve stimulation was excellent. CONCLUSIONS: Our study provides normative values of phrenic nerve motor responses in a large cohort of healthy subjects and identifies age and sex as factors of variation. Muscle Nerve 59:451-456, 2019.

A 12-week combination of clarithromycin and prednisone compared to a 24-week prednisone alone treatment in cryptogenic and radiation-induced organizing pneumonia.

Background: Some data suggest that anti-inflammatory macrolides may be effective to treat organizing pneumonia (OP) and prevent relapses, but no formal comparison with prednisone alone is available. To explore this issue, we retrospectively compared the efficacy of a 12-week combined regimen of clarithromycin and prednisone with a 24-week prednisone alone regimen in OP. Methods: A standard 12-week regimen of combined clarithromycin and prednisone was designed for the treatment of cryptogenic or radiation-induced OP, aiming at reducing the cumulated prednisone dose and the relapse rate. Its use was left to the discretion of the treating physicians, members of the Groupe d'Etudes et de Recherche sur les Maladies Orphelines Pulmonaires. Data were compared to a historical control group treated with a standard 24-week prednisone alone regimen. Results: 16 patients were treated with combined therapy and 21 with prednisone alone. Complete radiological remission was achieved in 63% of the combined therapy group and 81% of the prednisone alone group (p=0.38). Symptomatic relapses occurred in 81% of the combined therapy group, and 52% of the prednisone alone group (p=0.14). No side effect of clarithromycin was reported. Conclusions: In patients with cryptogenic or radiation-induced OP, a 12-week regimen of clarithromycin and prednisone showed no benefit on remission rate and relapse rate as compared to a 24-week prednisone only regimen. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 230-238).

An extremely rare case of postpartum gestational choriocarcinoma with long-term survival.

Gestational choriocarcinomas are highly malignant tumors with elevated serum human chorionic gonadotropin (hCG) levels. We report an extremely rare case of a 27-year-old woman who presented 4 months after normal delivery, with pulmonary, renal and intracardiac metastases of a choriocarcinoma. No primary uterine tumor was found. She was surgically treated for the renal and cardiac metastases as well as with cisplatin-etoposide chemotherapy. No recurrence has been observed 16 years after initial diagnosis, and the patient was able to have a second child. This case report shows that appropriate treatment of metastatic gestational choriocarcinoma can cure the patient without compromising her fertility.

Relationship between blood eosinophils, clinical characteristics, and mortality in patients with COPD.

In patients with COPD, there is controversy regarding the association of blood eosinophil (Eos) levels with 1) exacerbation frequency and 2) the effect of inhaled corticosteroids for prevention of exacerbations. To determine whether Eos define subgroups of patients exhibiting attributes of COPD clinical phenotypes, we compared clinical features and mortality rates in COPD patients from the Initiatives BPCO French cohort categorized using different thresholds of blood Eos levels. The following data were collected at inclusion: medical and smoking history, occupational exposures, dyspnea, cough and sputum production, exacerbations in the previous year, history of allergy and asthma, nasal symptoms, body mass index, St George Respiratory Questionnaire (SGRQ) total score, post-bronchodilator spirometry, comorbidities, and medications. Three-year survival between groups was compared using Kaplan-Meier analysis. Three sets of analyses were performed to compare patients with ≥2% versus <2%, ≥3% versus <3%, and ≥4% versus <4% Eos. Eos was available in 458 patients (mean age: 62 years, 72% male, mean forced expiratory volume in 1 second: 51% pred), including 235 patients with Eos ≥2% (49%), 149 with Eos ≥3% (33%), and 90 with Eos ≥4% (20%). For all cutoffs, there was no difference between Eos+ and Eos- groups in univariate analyses except for diabetes and SGRQ score (more frequent and more impaired, respectively, in lower Eos categories). In particular, there was no difference in exacerbation rate, history of asthma, or three-year survival. In conclusion, regardless of the cutoff, Eos+ COPD patients exhibited no specific characteristic in terms of symptoms, lung function, exacerbation rate, and prognosis. These findings suggest that the association of higher Eos with exacerbations reported in previous studies could be population specific, which does not support generalizing the use of Eos as a biomarker for COPD phenotyping.

Home care organization impacts patient management and survival in ALS.

OBJECTIVE: Progression of amyotrophic lateral sclerosis (ALS) depends on several factors linked to the disease. However, both the patient's living place and care organization role need to be evaluated. METHODS: We analysed the effect on survival of factors linked to ALS or the socio-geographical context in a prospective cohort of 203 patients followed between 2003 and 2011. RESULTS: Patients were 97 females and 106 males with a mean age of 65.5 years. Survival was longer in younger patients, in case of upper limb involvement, longer time to diagnosis, and initially higher forced vital capacity. Non-invasive positive pressure ventilation (NIPPV) and percutaneous gastrostomy (PEG) failed to demonstrate benefit. Patients who lived at home had longer survival. The nature of non-medical organization at home statistically influenced survival, which was longer with an organized network than with an unorganized one and shorter in absence of non-medical organization. In patients with indication of PEG and NIPPV, the proposition was statistically different according to the care givers. CONCLUSIONS: Besides the natural history of ALS, survival depended on home organization and the presence or the nature of a home-care system. Home organization was an important factor of decision for NIPPV and PEG proposals.

Impact of current cough on health-related quality of life in patients with COPD.

BACKGROUND: Cough and sputum production are frequent in chronic obstructive pulmonary disease (COPD). The objective of this study was to examine the relationship between cough and sputum production and health-related quality of life in COPD. METHODS: A cross-sectional study was conducted in the French Initiatives COPD cohort and assessed cough and sputum production within the past 7 days using the cough and sputum assessment questionnaire (CASA-Q), health-related quality of life, spirometry, smoking status, dyspnea, exacerbations, anxiety and depression, and comorbidities. RESULTS: One hundred and seventy-eight stable COPD patients were included (age, 62 [56-69] years, 128 male, forced expiratory volume in 1 second [FEV1]: 57 [37-72] % predicted) (median [Q1-Q3]). In univariate analyses, health-related quality of life (Saint George's respiratory questionnaire total score) was associated with each CASA-Q domain and with chronic bronchitis, exacerbations, dyspnea, FEV1, depression, and anxiety. All four domains introduced separately were independently associated with health-related quality of life. When introduced together in multivariate analyses, only the cough impact domain remained independently associated with health-related quality of life (R2=0.60). With chronic bronchitis (standard definition) instead of the CASA-Q, the R2 was lower (R2=0.54). CONCLUSION: This study provides evidence that current cough in the previous 7 days is an important determinant of health-related quality of life impairment in stable COPD patients.

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.

Determination of normal values for an isocapnic hyperpnea endurance test in healthy individuals.

Respiratory Muscle Endurance (RME) is an alternative way to assess respiratory muscle impairment but normal values are lacking to use this test in a clinical perspective. Our objective was then to determine reference values of RME in healthy subjects. We recruited 161 healthy subjects (25-80 years old) who were distributed within 5 groups with a 10-year range. We measured vital capacity (VC) and maximal respiratory pressure (MIP, MEP). The RME test consisted of isocapnic hyperpnea at increasing levels of ventilation until exhaustion to determine Tlim (expressed in minutes and as percentage of maximal voluntary ventilation, MVV). A significant difference between age-groups was observed for both VC and MEP expressed as percentage of predicted value. Mean Tlim was 21.8±5.9min [95% confidence interval 20.9-22.8], 74.4±15.9% of predicted MVV [95% CI 71.8-76.9]. Tlim was similar among age groups. Tolerance to the RME test was excellent. This study provides normal values of RME in a large age range of healthy subjects and demonstrates that RME is preserved in the elderly.