[French practical guidelines for the diagnosis and management of IPF - 2021 update, full version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version intégrale.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

[French practical guidelines for the diagnosis and management of IPF - 2021 update, short version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version courte.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

Benefit of continuous positive airway pressure on work quality in patients with severe obstructive sleep apnea.

BACKGROUND: The objective of this prospective study was to assess the effect of CPAP therapy on job productivity and work quality for patients with severe obstructive sleep apnea (OSA). METHODS: A convenience sample of patients diagnosed with severe OSA using polysomnography or polygraphy and with a therapeutic indication for CPAP was enrolled in our study. Patients completed two self-administered questionnaires: the first before CPAP therapy and the second during the first 6 months after CPAP treatment. OSA symptoms were evaluated through self-administered questionnaires assessing potential effects on occupational activity: excessive daytime sleepiness was rated by the Epworth Sleepiness Scale (ESS), emotional status was rated by the Hospital Anxiety and Depression (HAD) scale, work quality was rated by the Work Role Functioning Questionnaire (WRFQ). RESULTS: Forty patients (30 men, mean age 47.3 ± 8.3, mean BMI 31.6 ± 7.4, mean apnea-hypopnea index 51.8 ± 16.3) showed a beneficial effect of CPAP therapy on ESS score (mean 11.6 to 8.2, p < 0.0001), the anxiety dimension (mean 57.5% to 20%, p = 0.0002), and the overall anxiety-depressive score (mean 50% to 22.5%, p = 0.0006). Mean WRFQ scores were significantly improved in the second questionnaire for the dimensions of timetable requirements (69.3% to 83.5%, p < 0.0001), productivity requirements (71.4% to 82.2%, p < 0.0001), mental requirements (72.0% to 84.3%, p < 0.0001), and social requirements (82.6% to 91.4%, p < 0.003). CONCLUSIONS: We observed that adherence to CPAP therapy for patients with severe OSA mitigates the impact of symptoms on work including excessive daytime sleepiness, impairment of work ability, and anxiety and depressive disorders.

[Interstitial lung diseases from autoimmune origins: A prognostic and diagnostic challenge for the clinician]. / Pneumopathies interstitielles diffuses aiguës d'origine auto-immune : un défi diagnostique et pronostique pour le clinicien.

Acute or subacute interstitial lung diseases from autoimmune origins are especially hard to diagnose but have to be detected promptly. We illustrate this necessity with three case reports. One case of paraneoplasic polymyositis, one case of interstitial lung disease caused by a connectivite and one case of interstitial lung disease related to an anti-synthetase syndrome. The subject is to alert the practitioners to the early search of extra pulmonary signs, autoantibodies analysis in the objective to set up quickly the right treatment.

[Aspirin hypersensitivity: characteristics and diagnostic approach]. / Intolérance à l'aspirine : caractéristiques et éléments diagnostiques.

INTRODUCTION: In routine medical practice, the diagnosis of aspirin hypersensitivity (AH) remains difficult. No clinical feature or biomarker is available to reliably confirm this diagnosis and oral provocation tests (OPT) are rarely performed. AIM: To compare asthmatics with and without AH. METHOD: The clinical characteristics of 21 asthmatics with and 24 without AH respectively were determined. AH was defined by a positive OPT. A full blood count was done before and 24 hours after the OPT. RESULTS: The medical history was associated with a weak sensitivity (52%) and a good specificity (96%) for assessing the diagnosis of AH. There was a higher prevalence of AH in women, and a higher frequency of allergic rhinitis in AH, but no characteristic was useful to facilitate the diagnosis of AH in asthmatic patients. Our results demonstrate higher values of platelets in AH patients. Following OPT, in AH patients only, a decrease in blood eosinophils and an increase in neutrophils was observed. CONCLUSIONS: These results confirm that the diagnosis of AH is challenging, with the history having only weak sensitivity. The observation that fluctuations in eosinophils and neutrophils occur following OPT in AH patients only warrants further investigations and suggests a rapid pro-inflammatory role for aspirin.

[Deliberate interruptions and changes of dose of inhaled corticosteroids by asthma patients: "a community pharmacy study"]. / Interruptions et changements de posologie des corticoïdes inhalés par les patients asthmatiques: "enquête en pharmacie ".

BACKGROUND: Adherence to inhaled corticosteroids (ICS) remains a major issue for asthma management, even among patients receiving a regular prescription from their doctor. The frequency of deliberate interruption of ICS, and of spontaneous changes of dose, were studied in a population of asthma patients recruited in community pharmacies. METHODS: Asthma patients (aged 18-50) recruited in community pharmacies reported in self-administered questionnaires their spontaneous interruptions and changes of doses of ICS during the past 3 months. The characteristics of patients who interrupted their therapy or who modified the dose were compared with other patients. RESULTS: The studied population included 252 patients (mean age 35 year-old, females: 59%), of whom 62% had inadequately controlled asthma. Among these patients, 25% had interrupted ICS therapy during the past 3 months, while 21% spontaneously changed the dose. The most reported reason for interrupting ICS was the cessation of symptoms (50%). In multivariate analysis, interrupting ICS was mainly associated with inadequate asthma control (OR=3.1, 95% CI 1.5-6.4), while the strongest association with changing ICS doses was the patients' perception of asthma as a concern in their lives (OR=3.2, 95% CI 1.2-8.4). CONCLUSION: These results underline a poor understanding of the purpose of ICS therapy by patients. They also highlight the need of therapeutic education to improve the management of the disease.

Prone position in mechanically ventilated patients with severe acute respiratory failure.

The purpose of this study was to characterize changes in oxygenation, expressed as PaO2/F(I)O2, when patients with severe acute respiratory failure (PaO2/F(I)O2 < 150), unrelated to left ventricular failure to atelectasis, were turned to and from a supine to prone position at 1- and 4-h intervals. Ventilator settings were unchanged. Thirty-two consecutive patients were studied 1 h before, 1 and 4 h during and 1 h after placing in a prone position with PaO2/F(I)O2 of 103 +/- 28, 158 +/- 62, 159 +/- 59, and 128 +/- 52, respectively (ANOVA, p < 0.001). After 1 h in a prone position, improvement of PaO2/F(I)O2 by 20 mm Hg or more was considered a positive response. Seven patients studied had no response (22%), hereafter referred to as nonresponders, and 25 had a positive response (78%), hereafter referred to as responders. Among the seven nonresponders, two did not tolerate the prone position and were returned supine before the end of the 4-h trial. With the remaining five, PaO2/F(I)O2 evolution was 83 +/- 29, 77 +/- 19, 83 +/- 33, and 81 +/- 47, respectively. For two of the 25 responders, measurements are missing after returning to the supine position. In 10 of the 23 responders (43%) who completed the 4 h prone trial, the PaO2/F(I)O2 returned to its starting value when patients were repositioned supine: 117 +/- 24, 164 +/- 44, 156 +/- 55, and 110 +/- 34, respectively (ANOVA, p < 0.01). In 13 of the 23 (57%) improvement persisted: 105 +/- 27, 187 +/- 58, 189 +/- 49, and 157 +/- 49, respectively (ANOVA, p < 0.001). Repeated improvements after turning to a prone position were frequently observed. Side effects in the 32 patients after a total of 294 periods in a prone position included minor skin injury and edema, two instances of apical atelectasis, one catheter removal, one catheter compression, one extubation, and one transient supraventricular tachycardia.

[Pure embryonal carcinoma of the ovary. A review of the literature apropos of a case]. / Carcinome embryonnaire pur de l'ovaire. Revue de la littérature à propos d'un cas.

A 25-year-old woman with a stage IA pure embryonal carcinoma of the left ovary, without elevated serum markers namely AFP and HCG (nor-positive immuno-histologic marking at the later pathological analysis) underwent surgery alone (unilateral salpingo-oophorectomy). She relapsed seven weeks later with peritoneal carcinomatosis. She still did not have elevated tumor markers. She then received five courses of a cis platinum-based chemotherapy (bleomycin, etoposide and cisplatinum, BEP) and achieved pathological complete response (as attested by a coelioscopic third look). This response is still lasting, fourteen months after the end of the procedure. Malignant ovarian germ cells tumors account for 2 to 5% of all ovarian cancers and embryonal carcinoma is rare. It may be associated with high serum levels of AFP and/or HCG, but not when the embryonal carcinoma is really pure. These markers are very helpful for patient follow-up but not in our patient's history. These tumors offer a very good chemosensitivity especially when treated with cisplatinum. This treatment dramatically improved their prognosis and extensive debulking surgery is yet unnecessary. Some questions still remains is there any specificity for embryonal carcinoma within malignant germ cell tumors of the ovary group? What is the best treatment for stage IA disease? When is a surgical second look (or a third look as for our patient) justified?

Cisplatin and ifosfamide with various doses of vinorelbine (navelbine) in advanced non-small lung cancer.

From November 1992 to March 1994 we concluded a phase II trial of the combination of cisplatin 75 mg/m2 and ifosfamide 3 g/m2 on day 1 and increasing doses of vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France). Group A was given vinorelbine 25 mg/m2 on day 1, group B 25 mg/m2 on days 1 and 8, and group C 25 mg/m2 on days 1 and 15 and 12.5 mg/m2 on day 8. Inclusion criteria were histologically proven non-small cell lung cancer, stage IIIB or IV disease, no underlying disease, performance status < 2, no previous chemotherapy or radiotherapy, not older than 75 years, and informed consent. Treatment was given for 3 weeks. Eighty-six patients were included: 34 in group A, 28 in group B, and 24 in group C. One patient in group B was excluded because of false histology on review. Thirty-seven patients had stage IIIB and 48 had state IV disease, and 37 had squamous cell carcinoma, 32 had adenocarcinoma, and 16 had large cell carcinoma. The median age was 59.2 years (age range, 36 to 73 years). Evaluation was made 3 weeks after the third course of therapy. Thoracic radiotherapy (60 Gy) was given in stage IIIB disease; in stage IV disease, when an objective response was achieved, three additional courses of chemotherapy were given. The response rate after three cycles was 32% in group A, 44% in group B, and 67% in group C. Dose intensity, using Hryniuk's method, was the same for cisplatin and ifosfamide in the three groups. Dose intensity for vinorelbine was 8.1 mg/m2/wk in group A, 14.7 mg/m2/wk in group B, and 16.9 mg/m2/wk in group C. This study shows that increased dose intensity with vinorelbine is feasible and seems to increase the response rate and median survival, which was 28 weeks in group A and 38 weeks in group B. Median survival had not been reached in group C.

[Pulmonary cancer and recurrent arterial and venous thromboses]. / Cancer pulmonaire et thromboses artérielles et veineuses récidivantes.

Coagulation disorders frequently complicate cancer. We observed a patient with lung cancer who developed recurrent thromboembolism. Hypercoagulation was induced by tumor cells via different factors enhancing coagulation. Heparinotherapy, or in certain cases oral anticoagulants, are often ineffective.

Aerosolized interferon gamma for Mycobacterium avium-complex lung disease.

It has recently been shown that human alveolar macrophages can be selectively activated without systemic effect by the use of aerosolized interferon-gamma (IFN gamma), a cytokine that enhances macrophage oxidative and antimicrobial activity. We report the case of a 38-yr-old man negative for human immunodeficiency virus (HIV), with silicosis and advanced cavitary lung disease due to Mycobacterium avium intracellulare (MAI), who failed to improve despite 3 yr of continuous medical therapy with three or more drugs. He received three courses of aerosolized IFN gamma (500 micrograms 3 d per week for 5 wk in two courses and 200 micrograms 3 d a week for 5 wk after a short single trial of subcutaneous IFN gamma). The numbers of MAI decreased in the sputum during therapy, but cultures of the organism remained positive at the same level for the first two treatment periods. The patients sputum became AFB smear negative and the number of colonies decreased significantly after the third course of IFN gamma therapy. Cessation of IFN gamma was associated with a rapid increase in the numbers of MAI in the sputum. Aerosolized IFN gamma can be considered as an adjuvant to conventional drug therapy, with a good tolerance, in cases of lung disease caused by resistant MAI.

Lymphocytic bronchitis/bronchiolitis in a patient with primary biliary cirrhosis.

A 39 year old woman with severe primary biliary cirrhosis progressively developed exercise dyspnoea due to airflow obstruction. Sjögren's syndrome was not present. Bronchial and pulmonary biopsies demonstrated constrictive lymphocytic bronchitis/bronchiolitis, possibly a component of a generalized autoimmune process in this patient.

[Bronchiolo-alveolar carcinoma complicating myasthenia treated by azathioprine]. / Carcinome bronchiolo-alvéolaire compliquant une myasthénie traitée par azathioprine.

We report a case of broncho-alveolar carcinoma (CBA) in a man of 64 who had been treated with azathioprine for severe myasthenia gravis. The myasthenia was characterized by predominant involvement of the respiratory muscles, by resistance to anticholinesterase and by association with a thymoma without improvement after thymectomy. The CBA was associated with alveolar haemorrhage (HA) confirmed by lung biopsy and also by an infection due to Mycobacterium chelonae. The occurrence of HA in an immunodepressed patient is often due to an infection, notably aspergillosis. The role of CBA and the mycobacterial infections in the pathogenesis of HA is discussed. The use of azathioprine may lead to the occurrence of cancers, notably lung cancers, and also to haemopoietic neoplasia when doses of greater than 50 grams are used. We think that azathioprine may have contributed to the genesis of CBA in our patients.

[Interstitial fibrosing pneumopathy and dermatomyositis. Pulmonary histology and prognosis]. / Pneumopathie interstitielle fibrosante et dermatomyosite. Histologie pulmonaire et pronostic.

The authors describe a case of interstitial lung disease associated with dermatomyositis. Alveolar-interstitial shadowing on the initial chest X-ray, lymphocytosis on the broncho-alveolar lavage fluid, absence of anti-JO1 antibodies and presence of intra-alveolar buds on the open lung biopsy were observed. Our patient died of acute respiratory failure, 34 months after symptoms onset. Intra-alveolar buds found at an early stage of dermatomyositis interstitial lung disease, were associated with minimal interstitial cellularity, markedly interstitial fibrosis, poor prognosis and poor response to steroid therapy. In contrary, bronchiolitis obliterans organizing pneumonia noted at an early stage of interstitial lung disease associated with both dermatomyositis and polymyositis, seems to have better prognosis and response to corticosteroid, especially if associated with polymyositis.