French practical guidelines for the diagnosis and management of idiopathic pulmonary fibrosis - 2021 update. Full-length version.

BACKGROUND: Since the latest 2017 French guidelines, knowledge about idiopathic pulmonary fibrosis has evolved considerably. METHODS: Practical guidelines were drafted on the initiative of the Coordinating Reference Center for Rare Pulmonary Diseases, led by the French Language Pulmonology Society (SPLF), by a coordinating group, a writing group, and a review group, with the involvement of the entire OrphaLung network, pulmonologists practicing in various settings, radiologists, pathologists, a general practitioner, a health manager, and a patient association. The method followed the "Clinical Practice Guidelines" process of the French National Authority for Health (HAS), including an online vote using a Likert scale. RESULTS: After a literature review, 54 guidelines were formulated, improved, and then validated by the working groups. These guidelines addressed multiple aspects of the disease: epidemiology, diagnostic procedures, quality criteria and interpretation of chest CT scans, lung biopsy indication and procedures, etiological workup, methods and indications for family screening and genetic testing, assessment of the functional impairment and prognosis, indication and use of antifibrotic agents, lung transplantation, management of symptoms, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are intended to guide the diagnosis and practical management of idiopathic pulmonary fibrosis.

Sex differences in mandibular repositioning device therapy effectiveness in patients with obstructive sleep apnea syndrome.

PURPOSE: Mandibular repositioning devices (MRDs) are an effective treatment option for obstructive sleep apnea syndrome (OSAS), particularly in patients who refuse or cannot tolerate continuous positive airway pressure (CPAP). However, sex differences in the response to therapy and predictors of response are not clearly defined. This analysis of data from the long-term prospective ORCADES trial compared MRD efficacy in men and women with OSAS. METHODS: The ORCADES study included patients with newly diagnosed mild-to-moderate or severe OSAS who refused or were non-compliant with CPAP. MRD therapy was titrated over 3-6 months. The primary endpoint was treatment success (≥ 50% decrease in apnea-hypopnea index (AHI)). Complete response was defined using a range of AHI cut-off values (< 5/h, < 10/h, < 15/h). RESULTS: Overall treatment success rates were 89% in women and 76% in men (p = 0.019); corresponding rates in those with severe OSAS (AHI > 30/h) were 100% and 68% (p = 0.0015). In women vs. men, overall complete response rates at AHI cut-off values of < 5/h, <10/h, and < 15/h were 49 vs. 34% (p = 0.0052), 78 vs. 62% (p = 0.016), and 92 vs. 76% (p = 0.0032). On multivariate analysis, significant predictors of MRD treatment success were overbite and baseline apnea index in men, and neck circumference and no previous CPAP therapy in women. There were sex differences in the occurrence of side effects. Temporomandibular joint pain was the most common reason for stopping MRD therapy. CONCLUSIONS: MRD therapy was effective in women with OSA of any severity, with significantly higher response rates compared with men especially in severe OSAS. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01326143).

Delayed Bronchocutaneous Fistula Without Pneumothorax Following a Microwave Ablation of a Recurrent Pulmonary Metastasis.

Percutaneous tumor ablations are rather safe and effective treatments in selected patients for non-operable non-small cell lung carcinomas or lung metastases. However, there are major complications such as bronchopleural or bronchocutaneous fistula, which it is important to know in order to manage them safely. We describe in this report a case of bronchocutaneous fistula without pneumothorax following a microwave ablation of a recurrent pulmonary metastasis and its management.

Revisiting the systemic vasculitis in eosinophilic granulomatosis with polyangiitis (Churg-Strauss): A study of 157 patients by the Groupe d'Etudes et de Recherche sur les Maladies Orphelines Pulmonaires and the European Respiratory Society Taskforce on eosinophilic granulomatosis with polyangiitis (Churg-Strauss).

OBJECTIVE: To guide nosology and classification of patients with eosinophilic granulomatosis with polyangiitis (EGPA) based on phenotype and presence or absence of ANCA. METHODS: Organ manifestations and ANCA status were retrospectively analyzed based on the presence or not of predefined definite vasculitis features or surrogates of vasculitis in patients asthma, eosinophilia, and at least one systemic organ manifestation attributable to systemic disease. RESULTS: The study population included 157 patients (mean age 49.4±14.1), with a follow-up of 7.4±6.4years. Patients with ANCA (31%) more frequently had weight loss, myalgias, arthralgias, biopsy-proven vasculitis, glomerulonephritis on biopsy, hematuria, leukocytoclastic capillaritis and/or eosinophilic infiltration of arterial wall on biopsy, and other renal disease. A total of 41% of patients had definite vasculitis manifestations (37%) or strong surrogates of vasculitis (4%), of whom only 53% had ANCA. Mononeuritis multiplex was associated with systemic vasculitis (p=0.005) and with the presence of ANCA (p<0.001). Overall, 59% of patients had polyangiitis as defined by definite vasculitis, strong surrogate of vasculitis, mononeuritis multiplex, and/or ANCA with at least one systemic manifestation other than ENT or respiratory. Patients with polyangiitis had more systemic manifestations including arthralgias (p=0.02) and renal disease (p=0.024), had higher peripheral eosinophilia (p=0.027), and a trend towards less myocarditis (p=0.057). Using predefined criteria of vasculitis and surrogates of vasculitis, ANCA alone were found to be insufficient to categorise patients with vasculitis features. CONCLUSION: We suggest a revised nomenclature and definition for EGPA and a new proposed entity referred to as hypereosinophilic asthma with systemic (non vasculitic) manifestations.

Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg-Strauss).

The respiratory manifestations of eosinophilic granulomatosis with polyangiitis (EGPA) have not been studied in detail.In this retrospective multicentre study, EGPA was defined by asthma, eosinophilia and at least one new onset extra-bronchopulmonary organ manifestation of disease.The study population included 157 patients (mean±sd age 49.4±14.1 years), with a mean±sd blood eosinophil count of 7.4±6.4×109 L-1 at diagnosis. There was a mean±sd of 11.8±18.2 years from the onset of asthma to the diagnosis of EGPA, of 1.4±8.4 years from the first onset of peripheral eosinophilia to the diagnosis of EGPA, and of 7.4±6.4 years from EGPA diagnosis to the final visit. Despite inhaled and oral corticosteroid treatment, the severity of asthma increased 3-6 months before the onset of the systemic manifestations. Asthma was severe in 57%, 48%, and 56% of patients at diagnosis, at 3 years, and at the final visit, respectively. Persistent airflow obstruction was present in 38%, 30%, and 46% at diagnosis, at 3 years, and at the final visit, respectively.In EGPA, asthma is severe, antedates systemic manifestations by a mean of 12 years, and progresses to long-term persistent airflow obstruction despite corticosteroids in a large proportion of patients, which affects long-term management and morbidity.

Respiratory Conditions Associated with Tracheobronchomegaly (Mounier-Kuhn Syndrome): A Study of Seventeen Cases.

BACKGROUND: Mounier-Kuhn syndrome (MKS) is a rare disorder characterized by enlargement of the trachea and main bronchi and associated with recurrent respiratory tract infections. OBJECTIVE: This multicenter, retrospective study was carried out to describe respiratory conditions associated with tracheobronchomegaly. METHODS: Nine institutions involved in the 'Groupe d'Endoscopie de Langue Française' (GELF) participated in this study. A standard form was used to record patient characteristics, treatments and follow-up from medical charts. RESULTS: Seventeen patients, 53% male, aged 58 ± 18 years at diagnosis were included. Recurrent infections revealed MKS in 88% of cases. Main comorbid conditions were diffuse bronchiectasis in 88% of patients and tracheobronchomalacia in 67% of cases. The exacerbation rate was 1.5 exacerbations/patient/year. The main non-respiratory morbid condition was gastroesophageal reflux disease in 29% of cases. Interventional bronchoscopy was performed in seven patients (41%), consisting of laser (n = 2) and tracheal stenting (n = 5). Complications related to stents were observed in 80% of cases with a mean stent duration of 8 months. Four deaths, including three due to respiratory causes, occurred during follow-up. CONCLUSIONS: This is the largest series of MKS reported in the literature, showing that bronchiectasis and tracheobronchomalacia are the main associated morbid conditions that constitute a challenge for treatment.

Prescribed therapy for asthma: therapeutic ratios and outcomes.

BACKGROUND: Inhaled corticosteroids (ICS) are the cornerstone of asthma therapy. The ICS-to-total-asthma-medication ratios, calculated from claims data, indicate potentially risky disease management in asthma. Our aim was to assess the utility of ICS-to-total-asthma-medication ratios from primary care electronic medical records (EMRs) in detecting patients at risk of asthma exacerbation, as approached by prescription of oral corticosteroids and/or antibiotics. METHODS: Retrospective cohort studies were identified, using the Health Improvement Network general practice database (THIN, United Kingdom) and the Cegedim Longitudinal Patient Data (France). We selected asthma patients aged 16-40 years, with ≥ 4 prescriptions for asthma medications in 2007 and ≥ 1 prescription in 2008. For each country, three groups were defined according to ratio value in 2008: 0% (non-ICS users), <50% (low-ICS-ratio group) and ≥ 50% (high-ICS-ratio group). Outcomes were marker of asthma exacerbations: systemic corticosteroids and antibiotics. They were compared between groups in each country. RESULTS: Among 38,637 British and 4,587 French patients, higher numbers of prescriptions per patient of systemic corticosteroids, antibiotics and total asthma medications were observed in the low-ICS-ratio groups compared to other groups (p < 0.0001 for each outcome in both countries). Likewise, low-ICS-ratio patients had more medical contacts (p < 0.0001 in both countries), suggesting poorly controlled asthma. ICS-treated patients had lower risks of receiving systemic corticosteroids in 2008 in the high-ICS-ratio group, compared to the low-ICS-ratio group: RR = 0.54, 95%CI = [0.50-0.57] and RR = 0.78, 95%CI = [0.67-0.91] in the UK and France, respectively. CONCLUSIONS: Patients with high ICS-to-total-asthma-medication ratios presented fewer asthma-related outcomes. The low ICS-to-total-asthma-medication ratio calculated with EMRs data reflects insufficient prescribing of ICS relative to all asthma medications, which may lead to deteriorated asthma control.

Relative exposure to controller therapy and asthma exacerbations: a validation study in community pharmacies.

PURPOSE: "Controllers-to-total asthma drug" ratios computed from claims data identify asthmatics at risk of exacerbations. Direct link of ratios to data obtained from patients, such as control and recent outcomes, would facilitate their interpretation. We studied the relationship between R1 ratio (inhaled corticosteroids (ICS)/total anti-asthma drug ratio) and the Asthma Control Test. Comparisons were also conducted for secondary outcomes (asthma-related hospital contacts, monthly medical contacts, use of oral corticosteroids, and perception of disease burden). Results with R1 ratio were compared with those obtained with a second ratio, "ICS-plus-leukotriene receptor antagonist/total asthma drug" (R2 = ICS + leukotriene receptor antagonist/total anti-asthma drugs). METHODS: A survey was conducted in community pharmacies. Patients visiting with a prescription of anti-asthma drug and ≥12 months of drug dispensing recorded in the pharmacy were consecutively recruited. Dispensing data were linked to patient-reported outcomes. Asthma control and secondary outcomes were compared for both ratios between low-controller-ratio (R < 50%) and high-controller-ratio groups (R ≥ 50%), after excluding null values. RESULTS: Of the 919 eligible patients (mean age 37 years, 55% women), 90.2% and 92.4% had non-null values for R1 and R2, respectively. Compared with the low-controller-ratio groups, adjusted risks of being uncontrolled were significantly lower in the high-controller-ratio groups (RR = 0.64, 95%CI [0.54, 0.77] and RR = 0.57, 95%CI [0.47, 0.70], for R1 and R2 ratios, respectively). Likewise, fewer patients with secondary outcomes were observed in the high-controller-ratio groups, for both ratios. CONCLUSION: Asthma was better controlled among patients with high controller ratios, along with fewer asthma-related outcomes, for both R1 and R2 ratios. This confirms the utility of asthma/drug ratios in identifying patients at risk of exacerbations, notably in claims data.

Asthma drug ratios and exacerbations: claims data from universal health coverage systems.

In claims data, controller-to-total asthma drug ratios may reflect adequacy of disease management. We verified whether asthma patients with high ratios (≥ 50%) experienced fewer asthma-related outcomes. Two ratios were studied: that of the inhaled corticosteroids to total asthma drug (ICS/R03) and that of the inhaled corticosteroids plus leukotriene antagonist receptors-to-total asthma drug (ICS+LTRA/R03). Patients aged 13-40 years, with ≥ 3 respiratory drugs dispensed prescriptions in 2005 were selected from the French national claims data. After excluding null ratios, two groups were defined according to ratio values in 2007: low-ratio group (0% < ratio < 50%) and high-ratio group (ratio ≥ 50%). For both ratios, asthma-related outcomes and medical-resource utilisation were compared between groups. Of 2162 patients (mean age 27 years and 52% female), patients with non-null ratios were 81% and 85% for ICS/R03 and ICS+LTRA/R03 ratios, respectively. Patients with high ratios were less likely to receive oral corticosteroids than those in the low-ratio group (relative risk 0.79, 95% CI 0.72-0.88, and 0.80, 95% CI 0.72-0.88, for ICS/R03 and ICS+LTRA/R03, respectively). High ratio groups also presented fewer asthma-related hospitalisations. Significant negative correlations were also observed for both ratios, when studied quantitatively, according to patients' dispensed level of oral corticosteroids in 2007. In claims data, both ICS/R03 and ICS+LTRA/R03 ≥ 50% were related to fewer asthma-related outcomes. Ratios should be explored to identify asthma patients at risk of exacerbations. Low ratios can be considered as risk factors of exacerbation whatever the underlying cause.

Sarcoid-like granulomatosis and testicular germ cell tumor: the 'Great Imitator'.

OBJECTIVES: Only a few case reports and small case series of patients with sarcoidosis or sarcoid-like reaction and testicular germ cell tumors (GCT) have been reported in the literature. We performed a retrospective study of patients with testicular GCT managed at the Centre Léon-Bérard, who presented granulomatosis. METHODS: We performed a computerized search to identify all male patients with both a diagnosis of sarcoidosis or granuloma and testicular tumors seen at the Centre Léon-Bérard between 1992 and 2008. RESULTS: A total of 13 patients were identified among the 1,182 patients with testicular tumors. The median age at diagnosis of testicular GCT was 25.5 years. Six patients had stage I disease, 2 patients had stage IIb and 5 patients had stage III. Sarcoid-like granulomatosis was found in 9 patients at the time of initial diagnosis and in 4 patients during follow-up. Sarcoidosis presented mainly as pulmonary disease without severe organ involvement, with a benign evolution. CONCLUSION: We advise caution in the interpretation of clinical and histological findings in these patients. Sarcoid-like granulomatosis, a condition that can be combined with testicular cancer, should always be considered in the differential diagnosis of metastatic testicular tumors.

Correlates of adherence to respiratory drugs in COPD patients.

AIMS: To identify the correlates of accidental omissions and intentional interruptions of respiratory therapy in COPD. METHODS: COPD patients (GOLD stages II-IV) were recruited by general practitioners or respiratory physicians. Patients reported in self-report questionnaires their adherence to respiratory drugs (over the past three months) and their perception of therapy. RESULTS: 179 patients were included (mean age 63 years, 24% females). 45% forgot their respiratory therapy, while 30% interrupted it in the absence of any perceived benefit. The risks of accidental omissions were significantly higher when patients complained about having too many medications to take on a daily basis (OR=2.35; 95%CI=1.13-4.89), and among current smokers (OR=2.14; 95%CI=1.07-4.29). Females were more likely to interrupt therapy intentionally (OR=2.40; 95%CI=1.04-5.53). Surprisingly, there was no significant relationship with the number of drugs actually taken by patients. CONCLUSIONS: Adherence to respiratory drugs is inadequate in COPD patients. In order to improve adherence, patients' perception of the burden of therapy should not be overlooked.