Skin manifestations among GATA2-deficient patients.

GATA2 mutations have been identified in various diseases, such as MonoMAC syndrome, Emberger syndrome, familial myelodysplastic syndrome, acute myeloid leukaemia and dendritic cell, monocyte, B-cell and natural killer-cell deficiency. These syndromes present a wide range of clinical features, dominated by severe infections and haematological disorders such as myelodysplastic syndrome. Up to 70% of patients with GATA2 mutations have dermatological features, mainly genital or extragenital warts, panniculitis or erythema nodosum and lymphoedema. We report three patients presenting with common dermatological and haematological features leading to the diagnosis of GATA2 deficiency, but also with skin manifestations that have not been previously described: gingival hypertrophy, macroglossitis and glossitis and granulomatous lupoid facial lesions. Dermatologists can encounter patients with GATA2 mutations and should recognize this disorder.

Which patients should be tested for viruses on bronchoalveolar lavage fluid?

Bronchoalveolar lavage (BAL) is a major diagnostic tool in lung diseases, including viral respiratory infections. We aimed to better define the situations where viral tests should be performed on BAL fluid (BALF). We retrospectively studied all cases where viral tests [immunofluorescence, immunocytochemistry, viral culture, and/or polymerase chain reaction (PCR)] were performed on BALF during a period of 1 year (2008) in our institution. We compared the characteristics of patients with virus-positive versus virus-negative BALF. Of the 636 BALF samples sent to the microbiology laboratory, 232 underwent viral tests. Of these, 70 (30 %) were positive and identified 85 viruses: herpes simplex virus (HSV)-1 (n = 27), cytomegalovirus (CMV, n = 23), Epstein-Barr virus (EBV, n = 18), human herpesvirus (HHV)-6 (n = 12), respiratory syncytial virus (RSV, n = 3), rhinovirus (n = 1), and adenovirus (n = 1). The variables associated with positive viral tests on univariate analysis were immunosuppression [human immunodeficiency virus (HIV), corticosteroids >10 mg/day for ≥3 weeks, or other immunosuppressive therapy], ground-glass attenuations on computed tomography (CT) scanning, late-onset ventilator-associated pneumonia (VAP), and durations of (i) hospital stay, (ii) intensive care unit (ICU) stay, and (iii) mechanical ventilation before BAL (p < 0.01 for each comparison). On multivariate analysis, only immunosuppression [odds ratio (OR) 6.4, 95 % confidence interval (CI) [2.8-14.3], p < 0.0001] and ground-glass attenuations (OR 3.7, 95 % CI [1.8-7.7], p = 0.0004) remained associated with virus-positive BAL. None of the viral tests performed on BALF for the initial assessment of diffuse infiltrative lung disease (n = 15) was positive. PCR improved the diagnostic yield of viral tests on BALF by 50 %. Testing for viruses on BALF should be mostly restricted to immunocompromised patients with acute respiratory diseases and/or patients with unexplained ground-glass attenuations on CT scanning.

Human herpes virus co-infection is associated with mortality in HIV-negative patients with Pneumocystis jirovecii pneumonia.

The purpose of this investigation was to characterize the management and prognosis of severe Pneumocystis jirovecii pneumonia (PJP) in human immunodeficiency virus (HIV)-negative patients. An observational cohort study of HIV-negative adults with PJP documented by bronchoalveolar lavage (BAL) through Gomori-Grocott staining or immunofluorescence, admitted to one intensive care unit (ICU) for acute respiratory failure, was undertaken. From 1990 to 2010, 70 patients (24 females, 46 males) were included, with a mean age of 58.6 ± 18.3 years. The mean Simplified Acute Physiology Score (SAPS)-II was 36.9 ± 20.4. Underlying conditions included hematologic malignancies (n = 21), vasculitis (n = 13), and solid tumors (n = 13). Most patients were receiving systemic corticosteroids (n = 63) and cytotoxic drugs (n = 51). Not a single patient received trimethoprim-sulfamethoxazole as PJP prophylaxis. Endotracheal intubation (ETI) was required in 42 patients (60.0 %), including 38 with acute respiratory distress syndrome (ARDS). In-ICU mortality was 52.9 % overall, reaching 80.9 % and 86.8 %, respectively, for patients who required ETI and for patients with ARDS. In the univariate analysis, in-ICU mortality was associated with SAPS-II (p = 0.0131), ARDS (p < 0.0001), shock (p < 0.0001), and herpes simplex virus (HSV) or cytomegalovirus (CMV) on BAL (p = 0.0031). In the multivariate analysis, only ARDS was associated with in-ICU mortality (odds ratio [OR] 23.4 [4.5-121.9], p < 0.0001). PJP in non-HIV patients remains a serious disease with high in-hospital mortality. Pulmonary co-infection with HSV or CMV may contribute to fatal outcome.

Clarithromycin stops lung function decline in airway-centered interstitial fibrosis.

Airway-centered interstitial fibrosis (ACIF) is a distinct type of lung interstitial fibrosis characterized by lesions centered on the airways. Several cases reported in the literature showed little to no effect of corticosteroids and a high mortality rate in the absence of lung transplantation. No other efficient approach is described for the treatment of this type of fibrosis. We report for the first time the case of a 44-year-old patient diagnosed with ACIF on surgical lung biopsy and stabilized with clarithromycin after failure of systemic corticosteroids. We need to confirm this benefit in other patients to ascertain the anti-inflammatory effect of macrolides, which are far less harmful compared to corticosteroids or immunosuppressant drugs.

Spirometry practice by French general practitioners between 2010 and 2018 in adults aged 40 to 75 years.

In France, most spirometries are performed by pneumologists. Spirometry is difficult to access due to the distance to medical office and long delays for appointments. This lack of accessibility contributes to the underdiagnosis of chronic obstructive pulmonary disease (COPD) among patients aged between 40 and 75 years. In recent years, general practitioners (GPs) have been performing spirometry in private practice. However, the extent of this practice is unknown. A French retrospective, repetitive transversal study analysed data from the "Système National des Données de Santé" (SNDS) database. The targeted population was GPs in primary care that performed spirometries between 2010 and 2018, in patients aged between 40 and 75 years. Between 2010 and 2018, 302,674 (7.2%) spirometries were performed in France by GPs in private practices, in patients 40 to 75 years old. 5.4% by "expert GPs" (>60 spirometries/year) and 1.8% by "non-expert GPs". In "non-expert GPs" (2.8% of French GPs in 2018), the annual number of spirometries increased by 701 each year (p < 2.104), the annual number of GPs performing spirometries increased by 114 each year (p < 2.10-5). Overall, 24.9% of the spirometries performed by GPs were referrals from other GPs. The number of spirometries performed by GPs and the number of GPs performing spirometries has gradually increased over time. However, this increase is inadequate considering the need to early detect and follow up respiratory disorders.

Distinctive features between community-acquired pneumonia (CAP) due to Chlamydophila psittaci and CAP due to Legionella pneumophila admitted to the intensive care unit (ICU).

The spectrum of community-acquired pneumonia (CAP) due to Chlamydophila psittaci ranges from mild, self-limited CAP, to acute respiratory failure. We performed a retrospective study of 13 consecutive patients with CAP due to C. psittaci and 51 patients with legionellosis admitted in one intensive care unit (ICU) (1993-2011). As compared to patients with legionellosis, patients with psittacosis were younger (median age 48 [38-59] vs. 60 [50-71] years, p = 0.007), less frequently smokers (38 vs. 79 %, p < 0.001), with less chronic disease (15 vs. 57 %, p = 0.02), and longer duration of symptoms before admission (median 6 [5-13] vs. 5 [3-7] days, p = 0.038). They presented with lower Simplified Acute Physiology Score II (median 28 [19-38] vs. 39 [28-46], p = 0.04) and less extensive infiltrates on chest X-rays (median 2 [1-3] vs. 3 [3-4] lobes, p = 0.007). Bird exposure was mentioned in 100 % of psittacosis cases, as compared to 5.9 % of legionellosis cases (p < 0.0001). Extrapulmonary manifestations, biological features, and mortality (15.4 vs. 21.6 %, p = 0.62) were similar in both groups. In conclusion, severe psittacosis shares many features with severe legionellosis, including extrapulmonary manifestations, biological features, and outcome. Psittacosis is an important differential diagnosis for legionellosis, especially in cases of bird exposure, younger age, and more limited disease progression over the initial few days.

[Systemic sclerosis-related interstitial lung disease: Diagnostic and therapeutic strategy in the light of recent clinical trials]. / Pneumopathie interstitielle diffuse associée à la sclérodermie systémique : prise en charge diagnostique et thérapeutique à la lumière des essais thérapeutiques récents.

Systemic sclerosis (SSc) is an autoimmune disease associated to fibrotic manifestations. Interstitial lung disease (SSc-ILD), one of the main fibrotic features of SSc, is the first cause of SSc-related death. The management of SSc-ILD has recently benefited from the results of key randomised controlled trials. French authorities have approved Nintedanib for the treatment of SSc-ILD, and tocilizumab has recently been approved by the Food and Drug Administration (FDA) in the United-States (US). These recent approvals challenge the management of this fibrotic manifestation of SSc. This narrative literature review, at the crossroad of internal medicine and pulmonology, discusses what could be an up-to date approach, in terms of diagnostic and therapeutic strategies for SSc-ILD, in the light of the results from recent clinical trials.

[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.

[Hypersensitivity Pneumonitis: An update]. / Mise au point : pneumopathies d'hypersensibilité.

Hypersensitivity Pneumonitis (HP) is a common immune-mediated interstitial lung disease (ILD) induced by repeated exposure to environmental antigens in susceptible individuals. The most commonly known forms are bird fancier's disease and farmer's lung. However, the antigens involved are widely diverse. Therefore, the list of causes of HP is frequently expanding. HP seems to be under-diagnosed owing to its highly heterogeneous presentation in both the non-fibrotic and fibrotic subtypes and could represent up to 15% of all ILDs encountered in clinical practice. However, the recognition of HP cases is essential to ensure appropriate therapy for the patient. Home health care workers' intervention is sometimes critical in this context. In case of confirmed exposure, the diagnosis could be considered with high confidence if the high-resolution computed tomography (HR-CT) shows a typical HP pattern associated with a lymphocytosis over 30% in the broncho-alveolar lavage (BAL). In all other situations, the patients should undergo further investigations and additional histopathological sampling should be considered and submitted to a multidisciplinary team discussion. After diagnosis, antigenic eviction is the rule whenever possible. Corticosteroid treatment is the first-line medical treatment for severe forms and aims to prevent the development of fibrosis. Anti-fibrotic therapy is now an option for patients with progressive ILD and failure of immunomodulatory/immunosuppressive therapies.

[Ambulatory management of bilateral secondary spontaneous pneumothorax in palliative care]. / Prise en charge palliative ambulatoire d'un pneumothorax spontané secondaire bilatéral.

INTRODUCTION: Secondary spontaneous pneumothoraces account for 35% of all pneumothoraces after the age of 50. Their management is still debated and can be challenging due to the underlying respiratory condition. In our observation, the use of small-bore chest tubes allowed prolonged ambulatory care in a palliative setting. CASE REPORT: We report the case of a 54-year-old woman suffering from a leiomyosarcoma with multiple pulmonary metastases who had repeated episodes of pneumothorax, one of which was bilateral. Treatment involved the bilateral insertion of 8.5F pigtail catheters connected to Heimlich valves that allowed management as an outpatient. Recurrences were treated similarly, in association with oncological management, providing great additional benefits for patient comfort in this palliative context. CONCLUSION: Altogether, this case report confirms the applicability of outpatient management for drained spontaneous secondary pneumothoraces, even bilateral, especially in a palliative-care setting.

Idiopathic pulmonary fibrosis diagnosed concomitantly with diffuse squamous cell lung cancer on surgical lung biopsy: a case report.

BACKGROUND: Idiopathic pulmonary fibrosis is a disease with a poor prognosis and has been associated with increased lung cancer incidence. CASE PRESENTATION: We report the case of a Caucasian 75-year-old woman, a former smoker, hospitalized for breathlessness with a chest computed tomography scan showing an interstitial lung disease. A surgical lung biopsy was performed, confirming a pattern of usual interstitial pneumonia but also numerous disseminated foci of well-differentiated focally invasive squamous cell carcinoma without hypermetabolic lung nodule, mass, or enlarged lymph node visualized on chest computed tomography or positron emission tomography scan. Nintedanib was started for its antifibrotic and antitumor properties, without any other antineoplastic treatment. Three years after initiation of nintedanib, clinical, functional, and computed tomography scan evaluations were stable, and there was no evidence for evolution of the squamous cell carcinoma. CONCLUSIONS: Data are scarce regarding the benefit of nintedanib in patients with idiopathic pulmonary fibrosis-associated lung cancer, and it is unclear whether nintedanib could have a preventive role in lung carcinogenesis in idiopathic pulmonary fibrosis patients. This experience could help the scientific community in case of similar incidental findings.

Chest CT in COVID-19 pneumonia: A review of current knowledge.

The current COVID-19 pandemic has highlighted the essential role of chest computed tomography (CT) examination in patient triage in the emergency departments, allowing them to be referred to "COVID" or "non-COVID" wards. Initial chest CT examination must be performed without intravenous administration of iodinated contrast material, but contrast material administration is required when pulmonary embolism is suspected, which seems to be frequent in severe forms of the disease. Typical CT features consist of bilateral ground-glass opacities with peripheral, posterior and basal predominance. Lung disease extent on CT correlates with clinical severity. Artificial intelligence could assist radiologists for diagnosis and prognosis evaluation.

Incidence and characteristics of nosocomial influenza in a country with low vaccine coverage.

BACKGROUND: Influenza vaccination coverage is low in France, in at-risk patients and in healthcare workers. AIM: We aimed to estimate the incidence of nosocomial influenza, its characteristics and outcome. METHODS: During one influenza season, we retrospectively evaluated all cases of documented influenza. Inpatients with symptoms onset ≥48 h after admission were enrolled. Data were collected on a standardized questionnaire. RESULTS: From November 2017 to April 2018, 860 patients tested positive for influenza by polymerase chain reaction analysis on a respiratory sample. Among them, 204 (23.7%) were diagnosed ≥48 h after admission, of whom 57 (6.6% of all influenza cases) fulfilled inclusion criteria for nosocomial influenza: 26 women and 31 men, median age 82 years (interquartile range, 72.2-86.9). Twenty patients (38.6%) had recently (<6 months) received the seasonal influenza vaccine. Median time between admission and symptoms onset, and between symptoms onset and diagnosis were, respectively, 11 days (7-19.5) and 29 h (15.5-48). Influenza was mostly acquired in a double-bedded room (N = 39, 68.4%), with documented exposure in 14 cases. Influenza B virus was more common in nosocomial (46/57, 80.7%), than in community-acquired cases (359/803, 44.6%), P<0.001. Mortality rate at three months was 15.8% (N = 9). Incidence of nosocomial influenza was estimated at 0.22 per 1000 hospital-days during the study period. CONCLUSION: Nosocomial influenza is not rare in elderly inpatients, and may have severe consequences. Influenza B virus was over-represented, which suggests higher transmissibility and/or transmission clusters.

Idiopathic pulmonary fibrosis: Significance of the usual interstitial pneumonia (UIP) CT-scan patterns defined in new international guidelines.

INTRODUCTION: The new 2018 international guidelines for diagnosing usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) by CT scan split the old pattern possible UIP (2011 IPF guidelines) into two new patterns: probable UIP and indeterminate for UIP. However, the proportions and prognoses of these new CT-scan patterns are not clear. METHODS: We used a monocentric retrospective cohort of 322 patients suspected of having IPF (University Hospital of Rennes; Competence Center for Rare Lung Diseases; 1 January 2012-31 December 2017). All patients initially diagnosed by CT scan as possible UIP were included. The chest CT-scans were then reclassified according to the new 2018 international guidelines by 3 observers. These data were then subjected to survival analysis with multivariate Cox regression using a composite endpoint of death, lung transplantation, a decline of≥10% in forced vital capacity (FVC), or hospitalization. RESULTS: Of the 89 possible UIP patients included, 74 (83%) were reclassified as probable UIP and 15 (17%) as indeterminate for UIP. Probable UIP patients were more likely to meet the composite endpoint (56/74 [75.7%] vs. 5/15 [33%] patients; HR [IC 95%] =3.12 [1.24; 7.83], P=0.015). Multivariate analysis indicated that the probable UIP pattern was associated with significantly increased risk of reaching the composite endpoint (HR [95% CI]=2.85[1.00; 8.10], P=0.049). CONCLUSION: The majority of possible UIP diagnoses corresponded to probable UIP, which was associated with a significantly worse prognosis than indeterminate for UIP. This distinction between these two CT patterns emphasizes the relevance of the new international guidelines for the diagnosis of IPF.

Inflammatory biomarkers in airways of patients with severe asthma compared with non-severe asthma.

BACKGROUND: About 5-10% of patients with asthma suffer from poorly-controlled disease despite corticosteroid (CS) therapy. OBJECTIVE: We determined whether there were any differences in inflammatory biomarkers between severe and non-severe asthma patients. METHODS: Nineteen severe and 20 non-severe asthma patients were recruited and underwent collection of induced sputum, bronchoalveolar lavage (BAL) fluid and bronchial biopsies. RESULTS: Biopsy results showed no differences in eosinophils (major basic protein positive), neutrophils, macrophages, T cells and mast cells in the bronchial submucosa. However, subbasement membrane (SBM) thickness and smooth muscle area were increased in the biopsies. No significant differences were observed in the induced sputum inflammatory cells. In BAL fluid, there was a significant increase in neutrophils but a significant decrease in macrophages. Eosinophil counts were non-significantly increased threefold in both sputum and BAL in severe asthma. Levels of IL-8 and IL-13 in sputum supernatants were similar in both groups of asthma patients. There was a significant inverse correlation between post-bronchodilator forced expiratory volume in 1 s and provocative concentration of methacholine causing a 20% fall in FEV(1) with SBM thickness. CONCLUSION: Differences in inflammatory cells were observed mainly in terms of increased neutrophils and reduction in macrophage numbers in BAL fluid with a trend towards increased eosinophils in severe asthma compared with non-severe asthma. However, the most notable features are the increase in features of airway wall remodelling of SBM thickness and smooth muscle area.

[Features distinguishing ornithosis from avian acute hypersensitivity pneumonitis - a retrospective analysis]. / Pneumopathies et exposition aux oiseaux : ornithose ou pneumopathie d'hypersensibilité aiguë aviaire ?

INTRODUCTION: The aim of our study was to compare the features at diagnosis in patients with ornithosis to patients with avian acute hypersensitivity pneumonitis (HP). Clinical, biological and radiological differences could potentially help clinicians to distinguish these diseases. METHODS: We conducted a retrospective study on patients admitted from 2000 to 2016 in three hospitals. Ornithosis was diagnosed based on a positive polymerase chain reaction for Chlamydophila psittaci on respiratory samples and/or a seroconversion while HP was diagnosed on the basis of at least one positive serum precipitin. RESULTS: Twelve patients with HP and 13 patients with ornithosis were identified. Compared to HP, ornithosis occurred more frequently in males (P=0.047), with less previous respiratory diseases (P=0.01), shorter symptom duration (P=0.03), less frequently bilateral crackles (P=0.004), more severe disease requiring more frequently intensive care admission (P=0.005), higher CRP values (P=0.005) and more profound lymphopenia (P=0.02). Ground glass shadowing on CT scan (P=0.001) or bronchiectasis (P=0.03) were more frequently noted in patients with HP. CONCLUSIONS: Our results suggest that patients with ornithosis and HP have important differences in their clinical, biological, and radiological presentation.

[Hypersensitivity pneumonitis presenting as acute respiratory distress syndrome]. / Pneumopathie d'hypersensibilité révélée par un syndrome de détresse respiratoire aiguë.

INTRODUCTION: Hypersensitivity pneumonitis (HP) are typically subacute in their presentation and the diagnosis may be difficult. METHOD: We report a case of a hypersensitivity pneumonitis in a 27-years-old woman, caused by exposure to mould in an insalubrious mobile home. The initial presentation was with acute respiratory distress syndrome complicating RSV pneumonia, treated with ribavirin and corticosteroids in winter 2013-2014. The diagnosis of hypersensitivity pneumonitis was based on clinical and radiological relapse occurring during winter 2014-2015 with confirmed exposure to antigen with fungal sampling at home, respiratory deterioration with antigen rechallenge and a compatible chest CT-scan. CONCLUSION: The diagnosis of hypersensitivity pneumonitis should be considered in similar cases. Treatment is based mainly on removing exposure to the causative antigen.