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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]

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]

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: 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]

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.