Antonio M. Vignola

Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with concomitant allergic asthma and persistent allergic rhinitis: SOLAR

Background:  Anti‐IgE therapy could be particularly beneficial for patients with concomitant disease as it targets a common factor in both diseases. The aim of this study was to evaluate the efficacy and safety of omalizumab in patients with concomitant moderate‐to‐severe asthma and persistent allergic rhinitis.

Links between rhinitis and asthma.

There is compelling evidence of a close relationship between the upper and lower airways in asthma and rhinitis. Rhinitis is present in the majority of patients with asthma, and a significant minority of patients with rhinitis have concomitant asthma. Similarities between the two conditions occur in the nature of the inflammation present in the target tissues. A common initiating step in the inflammatory process of allergic airways disease is the presence of immunoglobulin E providing an adaptor molecule between the offending allergen and inflammatory cell activation and mediator release. Differences in the two conditions arise largely from the structural differences between the nose and the lungs. In an asthmatic, concomitant allergic rhinitis increases healthcare costs and further impairs quality of life. The presence of rhinitis should always be investigated in children and young adults with asthma. Subjects with allergic rhinitis have an increased risk of developing asthma and may form a suitable population for secondary intervention to interrupt the ‘allergic march’.

Evaluation of apoptosis of eosinophils, macrophages, and T lymphocytes in mucosal biopsy specimens of patients with asthma and chronic bronchitis

BACKGROUND Apoptosis regulates inflammatory cell survival, and its reduction contributes to the chronicity of an inflammatory process. Apoptosis is controlled by suppressing or inducing genes, such as bcl-2 and p53, respectively. OBJECTIVE We sought to assess apoptosis of eosinophils, macrophages, and T lymphocytes in bronchial biopsy specimens from asthmatic subjects and to examine its regulation by evaluating the expression of B-cell lymphoma leukemia-2 (Bcl-2) and P53 proteins. We also sought to explore the relationships between cell apoptosis and GM-CSF, a cytokine able to increase eosinophil and macrophage survival. METHODS Apoptosis in eosinophils, macrophages, and T lymphocytes was evaluated in bronchial biopsy specimens obtained from 30 asthmatic subjects, 26 subjects with chronic bronchitis, and 15 control subjects by combining the terminal deoxynucleotidyl transferase-mediated dNTP nick end-labeling technique and immunohistochemistry. The expression of P53, Bcl-2, and GM-CSF was studied through immunohistochemistry by using specific mAbs. RESULTS The number of apoptotic eosinophils and macrophages was lower in subjects with asthma than in those with chronic bronchitis (P <.007 and P <.001, respectively) and inversely correlated with the clinical severity of asthma (P <.001 and P <.002, respectively). Few T lymphocytes were apoptotic in all groups studied. In asthma GM-CSF+ cells correlated with the number of nonapoptotic eosinophils and macrophages (P =.0001) and with the severity of the disease (P <.003). In asthma Bcl-2+ cells were higher than in control subjects and subjects with chronic bronchitis (P <.002 and P <.015, respectively), they outnumbered P53+ cells, and they correlated with the number of T lymphocytes (P <.001) and with the severity of the disease (P <.003). CONCLUSION Airway inflammation in asthma is associated with an enhanced survival of different cell types caused by reduced apoptosis.

Standard skin prick testing and sensitization to inhalant allergens across Europe--a survey from the GALEN network

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA2LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15–20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA2LEN Pan‐European core SPT panel.

Allergic rhinitis, rhinosinusitis, and asthma: one airway disease

Asthma and allergies, including rhinoconjunctivitis and atopic dermatitis, are common throughout the world, with a high burden of morbidity and cost. The nasal and bronchial mucosa present similarities, and most patients with asthma also have rhinitis, suggesting the concept of one airway, one disease. Not all patients with rhinitis present with asthma, however, and there are differences between rhinitis and asthma. For this article, the authors differentiate between chronic rhinosinusitis and nasal polyposis based on the presence of polyps in the nasal cavity or the sinuses during clinical examination or surgery. This approach neglects an ill-defined group of chronic hyperplastic sinusitis, which might represent a transition phase.

Muscarinic receptors, leukotriene B4 production and neutrophilic inflammation in COPD patients.

Background:  Acetylcholine (ACh) plays an important role in smooth muscle contraction and in the development of airway narrowing; preliminary evidences led us to hypothesize that ACh might also play a role in the development of airways inflammation in chronic obstructive pulmonary disease (COPD).

Airway mucosal inflammation in COPD is similar in smokers and ex-smokers: a pooled analysis

Bronchial biopsy specimens from chronic obstructive pulmonary disease (COPD) patients demonstrate increased numbers of CD8+ T-lymphocytes, macrophages and, in some studies, neutrophils and eosinophils. Smoking cessation affects the rate of forced expiratory volume in one second (FEV1) decline in COPD, but the effect on inflammation is uncertain. Bronchial biopsy inflammatory cell counts were compared in current and ex-smokers with COPD. A pooled analysis of subepithelial inflammatory cell count data from three bronchial biopsy studies that included COPD patients who were either current or ex-smokers was performed. Cell count data from 101 subjects, 65 current smokers and 36 ex-smokers, were analysed for the following cell types: CD4+ and CD8+ T-lymphocytes, CD68+ (monocytes/macrophages), neutrophil elastase+ (neutrophils), EG2+ (eosinophils), mast cell tryptase+ and cells mRNA-positive for tumour necrosis factor-α. Current smokers and ex-smokers were similar in terms of lung function, as measured by FEV1 (% predicted), forced vital capacity (FVC) and FEV1/FVC. The results demonstrate that there were no significant differences between smokers and ex-smokers in the numbers of any of the inflammatory cell types or markers analysed. It is concluded that, in established chronic obstructive pulmonary disease, the bronchial mucosal inflammatory cell infiltrate is similar in ex-smokers and those that continue to smoke.

Pathophysiology of Allergic Rhinitis

Allergy rhinitis results from an IgE-mediated allergy associated with nasal inflammation of variable intensity. The mechanisms of allergic rhinitis have been clarified using nasal challenge with allergen or proinflammatory mediators and measuring cells and mediators released during the early- and late-phase allergic reaction. However, the priming effect of the nasal mucosa is of importance since a single challenge does not perfectly mimic the ongoing allergic reactions induced by repeated allergen exposure. In seasonal and chronic allergic rhinitis, the same cells and mediators are of importance but nonspecific nasal hyperreactivity develops. The regulation of the inflammation of allergic rhinitis is dependent on adhesion molecules and cytokines.

Effect of cilomilast (Ariflo) on TNF-α, IL-8, and GM-CSF release by airway cells of patients with COPD

Background: Inflammation in chronic obstructive pulmonary disease (COPD) is characterised by increased neutrophilic infiltration of the airways. Cilomilast, a novel selective phosphodiesterase 4 inhibitor in clinical development for COPD treatment, exerts anti-inflammatory effects. The ability of cilomilast to inhibit the release of neutrophil chemoattractants such as tumour necrosis factor (TNF)-α, interleukin (IL)-8, and granulocyte-macrophage colony stimulating factor (GM-CSF) by bronchial epithelial cells and sputum cells isolated from 10 patients with COPD, 14 normal controls, and 10 smokers was investigated. Methods: Bronchial epithelial cells obtained by bronchial brushing and sputum cells isolated from induced sputum samples were cultured for 24 hours in the presence or absence of cilomilast (1 μM). After incubation the supernatants were harvested and the levels of mediators measured by ELISA. Chemotactic activity in supernatants was also measured using a Boyden chamber. Results: TNF-α and IL-8 release by bronchial epithelial cells and sputum cells was higher in patients with COPD than in controls (p<0.0001) and smokers (p<0.0001). GM-CSF was only detectable in sputum cell supernatants and its level was higher in patients with COPD than in controls and smokers (p<0.0001, respectively). Cilomilast significantly reduced TNF-α release by bronchial epithelial cells and sputum cells (p=0.005) and GM-CSF release by sputum cells (p=0.003), whereas IL-8 release was not statistically inhibited. Supernatants of sputum cells and bronchial epithelial cells treated with cilomilast significantly decreased neutrophil chemotaxis (p<0.006 and p<0.008, respectively). Conclusions: Cilomilast inhibits the production of some neutrophil chemoattractants by airway cells. This drug may play a role in the resolution of neutrophilic inflammation associated with COPD and cigarette smoke.

Beclomethasone/formoterol vs fluticasone/salmeterol inhaled combination in moderate to severe asthma

Background:  Recommended treatment for moderate to severe asthma is the combination of an inhaled corticosteroid and a long‐acting beta2‐agonist. The present study was designed to compare a new fixed combination of extrafine beclomethasone and formoterol, with the fixed combination fluticasone and salmeterol.