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This review is the synthesis of a working group on mild asthma. Mild asthma includes intermittent and persistent mild asthma according to the Global Initiative for Asthma (GINA) classification, and affects between 50% and 75% of asthmatic patients. Mild asthma is more frequent, more symptomatic, and less well controlled in children than in adults. Cohort studies from childhood to adulthood show that asthma severity usually remains stable over time. Nevertheless, mild asthma can lead to severe exacerbations, with a frequency ranging from 0.12 to 0.77 per patient-year. Severe exacerbations in mild asthma represent 30–40% of asthma exacerbations requiring emergency consultation. In mild asthma, inflammation and structural remodelling are constant, of varying intensity, but nonspecific. Therapy with inhaled corticosteroids (ICS) decreases bronchial inflammation, but has only a slight effect on structural remodelling, and, when stopped, inflammation immediately recurs. Permanent low-dose ICS therapy is the reference treatment for persistent mild asthma. Effectiveness is to be reassessed at 3 months, and if it is insufficient the patient is no longer considered mildly asthmatic, and treatment has to be stepped up. As mild asthma is the most frequent form of the disease, diagnosis and management require physicians’ particular attention. [ABSTRACT FROM AUTHOR]

Background: Pressurized metered-dose inhalers (pMDIs) have traditionally used CFCs as propellants. However, the worldwide phase-out of CFCs has necessitated the development of new pMDIs that use alternative propellants. One such replacement is the hydrofluoroalkane HFA-134a. Objectives: This study sought to establish the clinical non-inferiority of a new HFA-134a-containing pMDI to a conventional dry powder inhaler (DPI) in the administration of formoterol to adult patients with moderate-to-severe, stable persistent asthma. The secondary aim was to collect safety data in a multiple-dose long-term study. Methods: During this multicenter, double-blind, parallel study, 500 patients were randomized to receive 12 μg of formoterol twice daily for 12 weeks via either an HFA pMDI or a DPI. If necessary, the dose could be increased to 24 μg twice daily. At baseline, all patients (aged 18–70 years) had an FEV1 40–80% of predicted and a documented positive response to the reversibility test. Results: After 12 weeks’ therapy, the adjusted mean morning PEFR was 343.69 l/min in the formoterol HFA pMDI group and 344.56 l/min in the formoterol DPI group. Because the lower limit of the 95% CI for the between-group difference (–11.64 l/min) was well within the non-inferiority margin (–20 l/min), the HFA device was deemed clinically non-inferior to the DPI device. This finding was confirmed when evening PEFR and FEV1 were assessed. Both formulations of formoterol were well tolerated during prolonged multiple dosing. Conclusions: This study provides evidence that the new HFA-formulated formoterol pMDI has a similar efficacy and safety profile to the conventional formoterol DPI in the treatment of patients with moderate-to-severe asthma. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: In asthma, inflammation affects both the proximal and distal airways and may induce significant hyperinflation (HI). This study sought to evaluate the prevalence of HI in asthmatic patients with poorly controlled disease and/ or dyspnea. Methods: Poor asthma control was defined by an Asthma Control Test (ACT) score <20 (n = 287), and dyspnea was defined as a modified Medical Research Council score ≥1 (n = 18). HI was defined as either a residual volume/total lung capacity (RV/TLC) above the upper limit of normal (RV-HI) or a functional residual capacity (FRC) >120% predicted (FRC-HI). HI reversibility after administration of salbutamol (400 lg) was defined as a decrease in RV >20% or a reduction in FRC >10%. Changes in dyspnea and chest tightness were evaluated on a visual analogue scale. Results: Both RV-HI and FRC-HI were observed in 48% of the 305 patients (mean ± SD age: 49 ± 17; FEV1: 75 ± 18% predicted) included in the study. The prevalence of HI was higher in patients with a FEV1 <60% predicted (93% for RV-HI and 71% for FRC-HI, vs 21% and 41% in patients with a FEV1 > 80%). In patients with HI, the ACT score was lower and chest tightness higher. HI reversibility was obtained in 38% of the asthmatics with FRC-HI and 29% of the asthmatics with RV-HI, whereas FEV1 reversibility was obtained in half of these patients. Conclusions: HI is highly prevalent in poorly controlled asthmatics suggesting small airway dysfunction and may represent an additional criteria for evaluating responsiveness to bronchodilators. [ABSTRACT FROM AUTHOR]

Background: The severity of lung disease varies widely in patients with cystic fibrosis (CF) who have the same type of mutations of the cystic fibrosis transmembrane regulator (CFTR) gene, suggesting involvement of "modifier" genes. The nitric oxide synthase 1 (NOS1) gene is a candidate for this role because exhaled nitric oxide (NO) is reduced in patients with CF and NOS1 activity contributes to transepithelial ionic transport, immune defence, and non-specific inflammation of the airways.Methods: Dinucleotide GT repeat polymorphism was studied in the 5' untranslated region of the NOS1 gene, immediately upstream from the transcription initiation site, in 59 patients with CF and 59 healthy controls.Results: Nineteen alleles of the NOS1 gene were identified according to the number of GT repeats (from 18 to 36) in the 5 untranslated region. Exhaled NO levels were significantly correlated with the number of GT repeats. Patients with CF who had the NOS1 genotype associated with high NO production had a slower decline in lung function during the 5 year follow up period. There was no confounding effect of age, chronic bacterial colonisation of the airway, or CFTR genotype.Conclusions: These data suggest a possible link between the NOS1 gene locus and the rate of decline in lung function in patients with CF. [ABSTRACT FROM AUTHOR]

Abstract: The 2nd French Clinical Vaccinology conference held on 20th April 2009 in Paris (France) was a unique opportunity to discuss basic and translational research in vaccinology and its implications for patients for respiratory diseases. This conference is organized by the Clinical Research Center Cochin-Pasteur, that has been involved for several years clinical research in vaccines. We report on here the key findings of the conference, especially the immunization of the chronic respiratory diseases, the clinical effectiveness of vaccines and the development of new vaccines in pulmonology. [ABSTRACT FROM AUTHOR]

Burgel P-R, Fajac I, Hubert D, Grenet D, Stremler N, Roussey M, Siret D, Languepin J, Mely L, Fanton A, Labbé A, Domblides P, Vic P, Dagorne M, Reynaud-Gaubert M, Counil F, Varaigne F, Bienvenu T, Bellis G, Dusser D. Non-classic cystic fibrosis associated with D1152H CFTR mutation. Background: Limited knowledge exists on phenotypes associated with the D1152H cystic fibrosis transmembrane conductance regulator ( CFTR) mutation. Methods: Subjects with a D1152H allele in trans with another CFTR mutation were identified using the French Cystic Fibrosis Registry. Phenotypic characteristics were compared with those of pancreatic insufficient (PI) and pancreatic sufficient (PS) cystic fibrosis (CF) subjects in the Registry (CF cohort). Results: Forty-two subjects with D1152H alleles were identified. Features leading to diagnosis included chronic sinopulmonary disease ( n = 25), congenital absence of the vas deferens ( n = 11), systematic neonatal screening ( n = 4), and genetic counseling ( n = 2). Median age at diagnosis was 33 [interquartile range (IQR, 24–41)] years in D1152H subjects. Median sweat chloride concentrations were 43.5 (39–63) mmol/l in D1152H subjects and were markedly lower than in PI and PS CF subjects (p < 0.05). Bronchiectasis was present in 67% of D1152H subjects, but Pseudomonas aeruginosa colonization and pancreatic insufficiency were present in <30% of subjects. Estimated rates of decline in forced expiratory volume in 1 s (FEV1) were lower in D1152H subjects vs PI CF subjects (p < 0.05). None of the D1152H subjects identified since 1999 had died or required lung transplantation. Conclusions: When present in trans with a CF-causing mutation, D1152H causes significant pulmonary disease, but all subjects had prolonged survival. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to determine whether the major nasal airway ion transport abnormalities in cystic fibrosis (that is, defective cAMP regulated chloride secretion and basal sodium hyperabsorption) are related to the clinical expression of cystic fibrosis and/or to the genotype. Methods: Nasal potential difference was measured in 79 adult patients with cystic fibrosis for whom clinical status, respiratory function, and CFTR genotype were determined. Results: In univariote and multivariate analysis, patients with pancreatic insufficiency were more likely to have low responses to low chloride (odds ratio (OR) 8.6(95% CI 1.3 to 58.5), p =0.03) and isoproterenol (OR 11.2 (95% CI 1.3 to 93.9), p = 0.03) solutions. Similarly, in univariate and multivariate analysis, patients with poor respiratory function (forced expiratory volume in 1 second <50% of predicted value) were more likely to have an enhanced response to amiloride solution (OR 3.7 (95% CI 1.3 to 11.0), p = 0.02). However, there was no significant relationship between nasal potential difference and the severity of the genotype. Conclusions: Nasal epithelial ion transport in cystic fibrosis is linked to the clinical expression of the disease. The pancreatic status appears to be mostly related to the defect in epithelial chloride secretion whereas the respiratory status is mostly related to abnormal sodium transport and the regulatory function of the CFTR protein. [ABSTRACT FROM AUTHOR]

Purpose. – The aim of the study was to assess the place of cardiac Magnetic Resonance Imaging (MRI) in patients with sarcoidosis with or without cardiac involvement.Material and methods. – Fifty patients with histologically-proven sarcoidosis underwent initial cardiac evaluation including MRI, ECG, holter ECG, echocardiography. Seven of them had cardiac involvement (cardiac insufficiency, auriculo-ventricular block, bundle-branch block). Fiveteen patients had a second evaluation at 10-month follow-up. MRI was classified in three stages, on the base of literature data (stage 1 “granulomatous”, stage 2 “exsudative”, stage 3 “fibrotic”).Results. – A good correlation between the type of the sarcoidosis and MRI was observed: patients with cardiac involvement had all stage 2 MRI; patients with quiescent sarcoidosis had normal or stage 3 MRI; patients without cardiac involvement had all stages on MRI. A good correlation was observed between cardiac MRI abnormalities and evolution of sarcoidosis. Patients under corticoid, with or without cardiac involvement all had regression of MRI lesions and sarcoidosis. In 2 cases, MRI was predictive of clinical cardiac involvement.Conclusion. – Cardiac MRI is a useful non-invasive method for the early diagnosis and follow-up of cardiac sarcoidosis. [Copyright &y& Elsevier]

Study Objectives: In dyspneic patients without left ventricular enlargement, it may be difficult to differentiate between obstructive lung disease and diastolic heart failure. Determination of plasma brain natriuretic peptide (BNP) levels, known to increase with ventricular stretch, may be of clinical relevance in this situation. We compared the discriminant power of BNP blood levels and of echocardiography in patients with either chronic obstructive lung disease or diastolic heart failure.Patients: Twenty-six New York Heart Association class III dyspneic patients with normal left ventricular systolic function were enrolled: 17 patients with chronic obstructive lung disease and 9 patients with unequivocal diastolic heart failure.Results: Echocardiographic data were unable to accurately differentiate between the two groups, whereas BNP levels were significantly and markedly higher in patients with diastolic heart failure when compared to those with obstructive lung disease (224 +/- 240 pg/mL vs 14 +/- 12 pg/mL, p < 0.0001).Conclusions: These preliminary results warrant a prospective, large-scale evaluation of the value of BNP assay for determining diastolic dysfunction, a common cause of dyspnea in elderly patients, and differentiating it from other diagnoses such as obstructive lung disease. [ABSTRACT FROM AUTHOR]

Airway inflammation represents a hallmark of the cystic fibrosis (CF) disease. However, the mucosal distribution of immune cells along the CF airways has not been clearly defined, particularly in intermediate bronchi and distal bronchioles. We analysed lung tissues collected at the time of transplantation from homozygous ΔF508+/+CF patients versus non-CF donors. Using immunohistochemistry, the distribution of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, polymorphonuclear neutrophils (PMN), mast cells, CD3+ T cells, including the CD4+ and CD8+ subsets, CD20+ B cells, CD38+ plasma cells and CD68+ macrophages, was analysed at lobar, segmental and distal levels of the bronchial tree. Using image cytometry, the number of cells per mm2 was assessed in the depth of the bronchial wall. In CF airways, alterations mainly consisted in lesions of the surface epithelium. Numerous immune cells were heterogeneously distributed all along the bronchial tree and mainly located in the mucosa, beneath the surface epithelium. Compared to non-CF donors, the lymphoid aggregates formed by B cells were significantly larger all along the CF airways (P = 0·001). The number of T lymphocytes was higher at the CF distal level (P = 0·035), where we observed an intense tissue damage. PMN preferentially accumulated (P = 0·033) in the CF surface epithelium, which overexpressed ICAM-1 but not VCAM-1 and E-selectin. These results highlight the nature of the inflammatory infiltrate in the CF airway mucosa and emphasize a prominent implication of PMN, B and T lymphocytes in the CF disease. [ABSTRACT FROM AUTHOR]

Background: Allergic asthma is a multifactorial and probably multigenic inflammatory disease of the upper airways, and has been associated with the HLA class II alleles DR4 and DR7. Here we investigated possible associations with other polymorphic susceptibility/resistance genes located within the major histocompatibility complex, i.e., the genes coding the major 70‐kDa heat‐shock proteins (HSP; Hsp70) hsp70–1, hsp70–2, and hsp70‐HOM, whose products are overexpressed in the bronchi of asthmatic patients. Methods: Genomic DNA was extracted from peripheral blood lymphocytes or buccal epithelial cells of 48 patients with allergic asthma and 31 selected nonatopic control subjects, in whom we previously reported a strong association of atopy with DR4/DR7 alleles.Results: No evidence was found for an independent role of hsp70 gene polymorphism in susceptibility to allergic asthma. However, hsp70 alleles might be involved in extended haplotypes of HLA markers. Conclusions: Our data suggest that Hsp70 overexpression in asthma results from complex interactions between environmental exposures and genetic background rather than from specific genetic variations in hsp70 genes. [ABSTRACT FROM AUTHOR]

Background Atopy, with or without associated asthma, provides a useful model for evaluating the genetic factors that control human immune responsiveness. HLA class II gene products are involved in the control of immune responses. Objectives We investigated whether susceptibility or resistance to the disease was associated with HLA class II genes. Methods Blood samples were obtained from two groups of unrelated European-born white adults: 56 atopic patients (52 of them with asthma) and 39 healthy controls with no personal or familial history of asthma or atopy. Genomic DNA was extracted from peripheral blood lymphocytes. The exons of DQA1, DQB1, DRB and DPB1 genes were selectively amplified by the polymerase chain reaction (PCR) method. Geno-typing was carried out by digestion of the amplified DNA products with allele-specific endonucleases (PCR-RFLP), which can recognize allelic variations in the polymorphic exon. Results We found no significant differences in the frequency of DPB 1 alleles between patients and controls. HLA class II DR4 and DR7 alleles were present in 39.2% of the patients and in 2.5% of the healthy subjects (Pc*2&les; 3.9 10-3). Conversely, DQA 1*0103 and DQB 1*0502 alleles were more frequent in the control subjects. These results confirm a previous study of an extended pedigree, which showed that DR4 and DR7 alleles were absent in all healthy members of the family and were frequently observed in atopic and/or in asthmatic subjects. Conclusion We observed that HLA-DR 4 and DR7 alleles are significantly implicated in their susceptibility to the disease and suggest that this susceptibility is more related to atopy than to specific responses to allergens. According to previous studies, we could also submit that in atopic patients with asthma, DR4 alleles at the least, could be more closely associated with atopy than with asthma per se. Conversely, we suggest that some allelic DQA 1 and DQB 1 sequences might confer protection against the disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: To determine the prevalence and clinical features of malnutrition and its relationship with the CFTR genotype in a cystic fibrosis (CF) adult population. DESIGN:: Cross-sectional study. SETTING:: Department of Pulmonology, Cochin Hospital, Paris, France. SUBJECTS:: 163 CF adults seen between 1997 and 1999. RESULTS:: Mean age was 28.8?y. Mean body mass index (BMI) was 19.1?kg/m2. Malnutrition (BMI<18.5?kg/m2) was seen in 81 patients (49.7%). Its severity was associated with diagnosis of CF before the age of 18?y (P<0.01), FEV1 values below 30%(P<0.01), the yearly decline of FEV1 (P<0.01), pancreatic insufficiency (P<0.01) and gastro-oesophageal reflux (P<0.01). Malnutrition was observed in 58.7%of patients with a severe CFTR genotype but in 28.6%of patients with a mild genotype (P<0.001). CONCLUSION:: Malnutrition remains frequent in adults with CF except in patients presenting with a mild CFTR genotype (leading to a mild phenotype and to later diagnosis). SPONSORSHIP:: None.European Journal of Clinical Nutrition (2005) 59, 152-154. doi:10.1038/sj.ejcn.1602039 Published online 15 September 2004 [ABSTRACT FROM AUTHOR]

Taking account of progress in understanding how cystic fibrosis (CF)-associated mutations cause a loss of CF transmembrane conductance regulator (CFTR) channel function, Michael Welsh and Alan Smith have classified CFTR mutations into five classes. Mutations of class I are mutations throughout the CFTR gene that produce premature termination signals because of splice-site abnormalities, frameshifts owing to insertions or deletions, or nonsense mutations. Class I mutations are expected to have a severe effect on protein function and have been associated with the severe pancreatic-insufficient phenotype. However, J.E. Mickle et al. described a nonsense mutation, S1455X, located in exon 24, which was associated with elevated sweat chloride concentrations in the absence of the CF phenotype in female compound heterozygotes. The 4382delA mutation is a frameshift deletion generating a stop codon - UGA - 15 amino acids downstream, and has been reported by M. Claustres et al. but without any clinical data. The compound heterozygous female for the 4382delA/F508del mutations was diagnosed as having CF at the age of 30 years, on the basis of bronchiectasis and a positive sweat test.

The article offers information on the study regarding the use of omalizumab for patients with allergic bronchopulmonary aspergillosis (ABPA) to diminish the use of systemic steroid therapy and the number of exacerbations. It says that ABPA is mostly seen in patients suffering from allergic asthma. Moreover, the study shows a reduction of the number of exacerbations and of the therapeutic load in ABPA patients treated by omalizumab without cystic fibrosis.

Discusses a case report on presumed hypersensitivity to minocycline and conjunctival infiltration. Description of minocycline as a prescribed systemic antibiotic for acne; Complexity of minocycline's mechanism of action; Use of minocycline for the treatment of rosacea.

Background A study conducted at Cochin Hospital in Paris showed that PICC lines were generally safe to infuse IV antibiotic courses at home for patients with Cystic Fibrosis (CF) and non-CF bronchiectasis (Burgel et al., 2014). However, in our CF centre, we have observed that dressing changes performed by free-lance nurses are oftentimes inadequate and inconsistent. In France, PICC lines have been used since 2005 and home care is provided by free-lance nurses who are responsible for their own training on PICC line care. Objectives To evaluate the skills and practice of free-lance nurses relating to PICC line care, particularly to identify the variables leading to improper PICC line dressing change. Methods A survey was conducted among free-lance nurses between March 2012 and January 2014. 296 self-administered questionnaires were filled by nurses at the beginning of IV therapy training sessions. Results 56.4% had already used a PICC line. 91.6% of them had changed the dressing at least once, 74.4% of which had changed the sutureless securement device (SSD) at least once (41.2% of the overall population). 41% found the SSD difficult to remove and to set up. 43.4% had been trained by private medical supply providers and 39.7% by hospital personnel. Nurses who had been trained were four times more likely to answer questions correctly and three times more likely to have the skills to follow practice guidelines. Conclusion This study enabled us to gain a better understanding of home care nursing practice, and to identify SSDs change as the main problem and therefore to tailor IV therapy training to the actual needs of free-lance nurses working in the home care setting. [ABSTRACT FROM AUTHOR]

Introduction et but de l’étude: Les études épidémiologiques soulignent la grande prévalence des problèmes nutritionnels et montrent qu’il est possible de les prévenir et, ainsi, d’améliorer le pronostic et l’espérance de vie des malades. Dans ce sens et afin d’optimiser la prise en charge des 300 patients adultes du Centre de Ressources et de Compétences de la Mucoviscidose (CRCM) Cochin, nous avons évalué leurs connaissances sur les liens entre maladie et alimentation, et sur la composition des aliments. Matériel et méthodes: Un questionnaire de 8 items a été remis par les diététiciennes aux patients hospitalisés et vus en consultation d’octobre à fin décembre 2006. Celui–ci portait sur les moyens d’information des patients, les causes possibles de perte de poids, les conséquences de l’insuffisance pancréatique exocrine (IPE), l’identification des aliments contenant des graisses, du calcium, l’équilibre d’un repas, la conduite à tenir pour enrichir, et la répartition des glucides en cas de diabète. Résultats: Parmi les 52 patients ayant répondu au questionnaire, 24 consultaient la diététicienne pour la première fois et 28 étaient déjà suivis. Leur moyenne d’âge est de 26 ans (18 à 46), avec autant de femmes que d’hommes. Leur IMC (indice de masse corporelle) moyen est de 19 (16 à 29), 84 % ont une IPE, 23 patients ont une intolérance aux glucides ou un diabète (18 déjà suivis, 5 nouveaux patients). Les patients (sans différence notoire entre les anciens et les nouveaux), ont peu de connaissances sur les liens entre leur maladie et l’alimentation. Nous avons par ailleurs constaté que de nombreux termes (ex : insuffisance pancréatique exocrine, reflux gastro oesophagien, occlusion.) sont inconnus pour la majorité d’entre eux. Les patients consultant pour la première fois ont peu de connaissances sur la composition des aliments en calcium et en lipides. Toutefois, dans les deux groupes, plus de la moitié considère qu’il n’y a pas de graisse dans la viande. 50 % des anciens patients sont capables d’équilibrer un repas contre 25 % des nouveaux patients. En moyenne 92 % des patients savent qu’il faut enrichir leur alimentation en cas de perte de poids mais seulement 64 % des anciens et 46 % des nouveaux savent par quels moyens. 83 % des patients diabétiques savent comment répartir les glucides sur la journée. Conclusions: Les patients ont besoin de temps pour assimiler les connaissances et mettre en place les conseils nutritionnels. Un suivi diététique régulier est nécessaire et l’éducation thérapeutique semble être adaptée dans la prise en charge nutritionnelle de la mucoviscidose. [Copyright &y& Elsevier]