Fabrice Paganin

Prognostic value of cluster analysis of severe asthma phenotypes

BACKGROUND Cross-sectional severe asthma cluster analysis identified different phenotypes. We tested the hypothesis that these clusters will follow different courses. OBJECTIVE We aimed to identify which asthma outcomes are specific and coherently associated with these different phenotypes in a prospective longitudinal cohort. METHODS In a longitudinal cohort of 112 patients with severe asthma, the 5 Severe Asthma Research Program (SARP) clusters were identified by means of algorithm application. Because patients of the present cohort all had severe asthma compared with the SARP cohort, homemade clusters were identified and also tested. At the subsequent visit, we investigated several outcomes related to asthma control at 1 year (6-item Asthma Control Questionnaire [ACQ-6], lung function, and medication requirement) and then recorded the 3-year exacerbations rate and time to first exacerbation. RESULTS The SARP algorithm discriminated the 5 clusters at entry for age, asthma duration, lung function, blood eosinophil measurement, ACQ-6 scores, and diabetes comorbidity. Four homemade clusters were mostly segregated by best ever achieved FEV1 values and discriminated the groups by a few clinical characteristics. Nonetheless, all these clusters shared similar asthma outcomes related to asthma control as follows. The ACQ-6 score did not change in any cluster. Exacerbation rate and time to first exacerbation were similar, as were treatment requirements. CONCLUSION Severe asthma phenotypes identified by using a previously reported cluster analysis or newly homemade clusters do not behave differently concerning asthma control-related outcomes, which are used to assess the response to innovative therapies. This study demonstrates a potential limitation of the cluster analysis approach in the field of severe asthma.

Adherence in severe asthma

Adherence in asthma is an important cause for concern. Although nearly 50% of asthma patients are considered poorly adherent to therapeutic advices, adherence is still difficult to assess, understand and improve despite major medical consequences. In this review, we revisited the literature of the last 10 years related to adherence in severe asthma. The concepts have changed and “compliance” is usually replaced by “adherence”. Assessment of adherence is addressing ethical issues, but provides important insight into difficult‐to‐treat asthma. Different tools have been used but none is routinely recommended. Health‐related outcomes (poor control, exacerbations, hospitalizations, lung function decline), which are clearly associated with severe asthma, are often worsened by non‐adherence with consequences also on patient related outcomes (quality of life). The potential behaviour associated with non‐adherence and all other related factors including easy‐to‐recognize psychological traits can help for patients future management. Therapeutic educational interventions have been recognized with a scientifically proven efficiency even though evolution and improvements are needed. A multidisciplinary approach is required in severe asthma. Therapeutic adherence for a given patient is always a prerequisite to any other aspects when addressing severe asthma phenotypes. Severe asthma should be considered only in those who still experienced poor asthma outcomes despite optimal adherence. At a glance, poor adherence and severe asthma should be considered antinomic. Better understanding of the causes and customised management are potential future directions.

Chikungunya à l’île de la Réunion: chronique d’une épidémie annoncée

Points essentiels Chikungunya est une maladie virale transmise par un moustique du genre Aedes. Actuellement elle sevit sur un mode epidemique a l’ile de la Reunion. Elle se caracterise essentiellement par un syndrome grippal mais associe a des polyarthralgies et une eruption. Le caractere invalidant et chronique des arthralgies est le fait clinique remarquable de l’infection a chikungunya. Il existe des formes graves et inhabituelles qui n’avaient jamais ete decrites dans la litterature. Ces formes doivent etre etudiees afin de pouvoir affirmer une relation directe entre le virus chikungunya et des facteurs de gravite. La therapeutique est uniquement symptomatique, associant antalgiques et/ou anti-inflammatoires. Il n’y a pas de vaccin. L’epidemie n’est pas circonscrite a l’ile de la Reunion car des cas de chikungunya ont ete declares dans les iles voisines (Maurice, Seychelles, Madagascar), un certain nombre de conseils doivent etre donnes aux voyageurs qui desirent venir dans la region.

Non-invasive assessment of small airway remodelling in smokers.

ABSTRACT Smoking associated COPD progression is likely to be directly linked to differential injury and repair dynamics in small airways (SA). Although IL8 is a well-accepted marker for injured airway epithelium, Clara cells [the predominant proliferating cells in SA] and SCGB1A1 protein [their major secretory product] have only recently emerged as potential SA repair markers. We therefore postulate that the SCGB1A1/IL8 ratio in the airways of smokers would be inversely associated with physiological, radiological and clinical measures of COPD. A cross-sectional cohort of 28 smokers undergoing surgery for peripheral nodule was recruited (24M/4F, age 61 ± 11 y, FEV1s 76 ± 20%, smoking 40 ± 12 p.y). SCGB1A1 and IL8 were measured by ELISA in the induced sputum (IS) 3 to 5 days prior to surgery as well as by immunohistochemistry from lung tissue (also assessed morphometrically) obtained distant to the cancer surgery site. COPD was assessed using standard clinical, functional and radiological parameters. Log-transformed IS-SCGB1A1 was linearly correlated with SCGB1A1-positive epithelial cells detected via immunohistochemistry (r = .533, p = .001), while IS-IL8 was positively related to SA infiltrating neutrophils (Elastase-positive cells). There was a striking negative correlation between IS-SCGB1A1/IL8 levels and whole airway thickness [SA < 2 mm] at morphometry (r = −0.83, p < 0.0001). IS-SCGB1A1/IL8 levels were also inversely associated with nitrogen slope [r = −0.52, p < 0.001] and HRCT SA score [r = −0.51, p < 0.001]. In a multivariate analysis the IS-SCGB1A1/IL8 ratio was a stronger predictor than both the physiological and radiological measures of SA disease assessed. The SCGB1A1/IL8 ratio measured in sputum is a potentially valuable biomarker for non-invasive assessment of SA remodelling in smokers.

A solitary bronchial papilloma with unusual endoscopic presentation: case study and literature review

BackgroundSolitary endobronchial papillomas (SEP) are rare tumors and most of them are described by case report. A misdiagnosis is common with viral related papillomas. A histopathological classification has recently permitted a major advancement in the understanding of the disease.Case PresentationWe report a case of a mixed bronchial papilloma with an unusual endoscopic presentation. The literature was extensively reviewed to ascertain the unusual characteristics of the current case. A 39-year of age male was referred to our institution for the investigation of a slight hemoptysis. Routine examination was normal. A fibroscopy revealed an unusual feature of the right main bronchus. The lesion was a plane, non-bleeding, non-glistering sub-mucosal proliferation. No enhanced coloration was noticed. Biopsies revealed a mixed solitary bronchial papilloma. In situ HPV hybridization was negative. Endoscopic treatment (electrocautery) was effective with no relapse.ConclusionThis lesion contrasts with the data of the literature where papilloma were described as wart-like lesions or cauliflower tumors, with symptoms generally related to bronchial obstruction. We advise chest physicians to be cautious with unusually small swollen lesions of the bronchi that may reveal a solitary bronchial papilloma. Endoscopic imaging can significantly contribute to the difficult diagnosis of SEP by pulmonary physicians and endoscopists.

Airway and Esophageal Stenting in Patients with Advanced Esophageal Cancer and Pulmonary Involvement

Background Most inoperable patients with esophageal-advanced cancer (EGC) have a poor prognosis. Esophageal stenting, as part of a palliative therapy management has dramatically improved the quality of live of EGC patients. Airway stenting is generally proposed in case of esophageal stent complication, with a high failure rate. The study was conducted to assess the efficacy and safety of scheduled and non-scheduled airway stenting in case of indicated esophageal stenting for EGC. Methods and Findings The study is an observational study conducted in pulmonary and gastroenterology endoscopy units. Consecutive patients with EGC were referred to endoscopy units. We analyzed the outcome of airway stenting in patients with esophageal stent indication admitted in emergency or with a scheduled intervention. Forty-four patients (58±\−8 years of age) with esophageal stenting indication were investigated. Seven patients (group 1) were admitted in emergency due to esophageal stent complication in the airway (4 fistulas, 3 cases with malignant infiltration and compression). Airway stenting failed for 5 patients. Thirty-seven remaining patients had a scheduled stenting procedure (group 2): stent was inserted for 13 patients with tracheal or bronchial malignant infiltration, 12 patients with fistulas, and 12 patients with airway extrinsic compression (preventive indication). Stenting the airway was well tolerated. Life-threatening complications were related to group 1. Overall mean survival was 26+/−10 weeks and was significantly shorter in group 1 (6+/−7.6 weeks) than in group 2 (28+/−11 weeks), p<0.001). Scheduled double stenting significantly improved symptoms (95% at day 7) with a low complication rate (13%), and achieved a specific cancer treatment (84%) in most cases. Conclusion Stenting the airway should always be considered in case of esophageal stent indication. A multidisciplinary approach with initial airway evaluation improved prognosis and decreased airways complications related to esophageal stent. Emergency procedures were rarely efficient in our experience.

Limited Short-term Steroid Responsiveness Is Associated With Thickening of Bronchial Basement Membrane in Severe Asthma

BACKGROUND The clinical manifestations of bronchial remodeling in asthma and the potential impact of this process on lung function remain unclear. We aimed to determine whether the presence of pathologic features of airway remodeling in patients with asthma was associated with steroid responsiveness in the short term. METHODS Sixty-three consecutive patients with severe asthma with chronic airflow impairment (post-bronchodilator FEV(1) < 80% predicted values) were recruited, clinically characterized, and had an initial bronchoscopy where endobronchial biopsy and BAL were performed. BAL cellular content was reported and reticular basement membrane (RBM) thickness was measured by validated repeated measures. Patients were then treated with 1 mg/kg/d of methyl prednisone, directly administered IV, for 10 days. A threshold of 15% FEV(1) improvement was used to discriminate responsive (group 1) and refractory patients (group 2). RESULTS Thirty-eight patients had a steroid responsiveness > 15% (group 1) and a thinner RBM at the biopsy level (5.78 ± 2.0 μm vs 7.60 ± 2.2 μm; P = .001) compared with nonsteroid responsive group 2 patients as defined. The best predictors for being unresponsive were no long-term treatment with oral steroids and increased RBM thickness. The associated receiver operating characteristic curve indicated that RBM thickness could predict steroid responsiveness below 15% with an area under the curve of 0.747 (P = .0002) at a threshold of 7 μm. CONCLUSIONS Features of airway remodeling are associated with limited short-term steroid responsiveness in severe asthma.

Pulmonary manifestations of leptospirosis

BACKGROUND Pulmonary manifestations in leptospirosis are considered a major complication and are related to a poor prognosis. We present a large series of patients with pulmonary involvement using a practical approach based on the presence of acute respiratory failure (ARF). METHODS A retrospective study of patients with confirmed leptospirosis. RESULTS One hundred and sixty-nine patients with a laboratory-confirmed diagnosis of leptospirosis were investigated. One hundred and thirty-four patients (36.7±14 years of age) had pulmonary involvement. Severe pulmonary involvement was defined by evidence of ARF. Univariate analysis found the following factors related to severe pulmonary leptospirosis: dyspnoea (OR=10.14, p<0.0001), pulmonary crepitations (OR=4.8, p<0.0004), abnormal chest X-ray (OR=9.88, p<0.007) with alveolar shadowing (OR=8.12, p<0.0001), oliguria/anuria (OR=5.48, p<0.0001), hepatomegaly (OR=7.11, p< 0.0001), shock (OR=8.38, p< 0.0001), ICU admission (OR=60.08, p< 0.0001), dialysis (OR=4.87, p< 0.001), mechanical ventilation (OR=216, p< 0.0001) and development of nosocomial infection (OR=21.5, p< 0.0001). The mortality rate was significantly different between severe (40%) and non-severe (5.3%) pulmonary forms (OR=11.87, p< 0.0001). Multivariate analysis found two independent factors related to severe pulmonary involvement: dyspnoea (OR=10.18, p< 0.0001) and oliguria/anuria (OR=4.87, p< 0.0009). We performed a multivariate analysis to assess independent factors related to mortality and found: mechanical ventilation requirement (OR=27.85, p< 0.0001) and AST greater than 150 IU/L (OR=4.57, p< 0.02). Haemoptysis was associated with survival (OR=0.2, p< 0.02). CONCLUSIONS Severe pulmonary involvement in leptospirosis is associated with extensive disease involving other organs. The association of multiple factors is associated with severe forms of the disease and a high mortality rate.

Manifestations pulmonaires de la leptospirose

Resume Introduction L’atteinte pulmonaire de la leptospirose est consideree comme une complication majeure. Nous presentons une serie de patients atteints de formes pulmonaires avec une approche pragmatique basee sur la presence d’une insuffisance respiratoire aigue (IRA). Methodes Analyse retrospective chez des patients avec un diagnostic formel de leptospirose. Resultats 169 patients ont ete investigues, 134 (36,7 ± 14 ans) avec atteinte pulmonaire ont ete analyses. Une atteinte pulmonaire severe etait definie par la presence d’une IRA. L’analyse univariee a retrouve comme facteur de severite : dyspnee (OR 10,14), crepitants (OR 4,8), radiographie thoracique anormale (OR 9,88), atteinte alveolaire (OR 8,12), oligo-anurie (OR 5,48), hepatomegalie (OR 7,11), choc (OR 8,38), admission en reanimation (OR 60,08), dialyse (OR 4,87), ventilation mecanique (OR 216), l’infection nosocomiale (OR 21.5). La mortalite etait differente entre les formes severes (40%) et non severes (5,3%) (OR 11,87). L’analyse multivariee retrouvait 2 facteurs independants lies aux formes pulmonaires severes : dyspnee et oligo-anurie. Une analyse multivariee a trouve les facteurs independants de mortalite : ventilation mecanique (OR 27,85), ASAT > 150 (OR 4,57). La presence d’hemoptysie etait protectrice (OR 0,2). Conclusions L’atteinte pulmonaire severe est associee a une maladie diffuse multi-organes. Les complications et le taux eleve de mortalite sont lies a de multiples facteurs.

Asthme à l’île de la Réunion : analyse de la sévérité et de la prise en charge thérapeutique

Resume Introduction L’asthme a la reunion est une pathologie frequente, mais il n’existe pas d’etude epidemiologique qui analyse la prevalence, la severite et la prise en charge des patients. Methodes Deux etudes ont ete realisees : une enquete de la CPAM et une analyse sur les donnees d’une consultation hospitaliere specialisee. Resultats 187 et 253 patients ont ete respectivement evalues. Nous retrouvons dans les 2 etudes 40 % de patients stratifies dans le groupe 3 du GINA (10 % en France metropolitaine). Le recours aux services d’urgence est frequent de meme que les admissions dans les services de reanimation. Il existe une sous-evaluation des patients par les medecins traitants qui ne classent pas correctement les asthmatiques. Cette sous-evaluation se retrouve dans les prescriptions therapeutiques avec l’utilisation de corticoides inhales chez 1/3 des asthmatiques des stades 2 et 3. Les mesures d’education sont mauvaises (30 % des patients ont une demonstration des systemes inhalateurs et 31 % ont eu une EFR). Conclusions Ces etudes montrent que le profil de la severite de l’asthme a la Reunion peut etre compare a celui des pays oceaniens (Australie, Nouvelle-Zelande) plutot qu’a la France metropolitaine. Une etude dans la population generale est necessaire afin de connaitre exactement la prevalence de l’asthme a l’Ile de la Reunion.