Contribution of Lung Fibroblast Migration in the Fibrotic Process of Airway Remodeling in Asthma

ABSTRACTBackgroundThe fibrotic process in airway remodeling of asthma may be characterized by an exaggerated deposition of extracellular matrix (ECM) components such as fibronectin and type I, III and IV collagen. In the present study, we established airway remodeling model mice and examined the mechanism of fibrotic change by measuring chemotactic activity of lung fibroblasts and quantifying collagen content in lung tissues.MethodsAirway remodeling model mice were made by ovalbumin (OA) sensitization and inhalation. Bronchoalveolar lavage (BAL) and bronchial biopsy were performed. Cell migration was assessed by the Boyden's chamber technique. The collagen content of lung tissue was measured using ELISA.ResultsThe chemotactic activity in lung fibroblasts toward the mouse BAL fluid (BALF) was significantly increased in OA-inhaled mice. Total soluble collagen content was significantly increased in OA-inhaled mice. We observed markedly increased collagen deposition around the airway wall in OA-inhaled mice, which was not shown in saline-inhaled mice. Furthermore, fibronectin in the BALF of OA-inhaled mice was significantly higher than that in the control mice.ConclusionsThe total soluble collagen content increased during the fibrotic change of airway remodeling in asthma. Furthermore, migration of fibroblasts may play a key role in this remodeling process, and fibronectin and type I and IV collagen seem to be chemotactic factors for the fibroblasts

The Relationship between Symptom Flare of Atopic Dermatitis and Airborne Japanese Cedar and Cypress Pollen Counts: A Self-Scoring Diary Study

Background. With an increase in Japanese cedar and cypress (JC) pollinosis, the relationship between JC pollen and atopic dermatitis (AD) has been studied. Some reports suggest that JC pollen can be one exacerbating factor for AD, but there has been no report that discusses JC pollen counts relating to AD symptom flare although actual airborne JC pollen counts can widely fluctuate throughout the pollen season. Objective. The relationship between symptom flare of AD and airborne JC pollen counts was examined. Methods. We monitored JC pollen counts in real time and divided the counts into low and high level. We then analyzed self-scored “itch intensity” recorded by 14 AD patients through a self-scoring diary. Results. Among the 14 patients, 7 had significantly higher itch intensity while the pollen counts were high. Conclusion. Even during the pollen season, actual airborne pollen counts can widely fluctuate. Our study suggested that symptom flare of AD could be influenced by the actual pollen counts

Reactivity of IgE in fish-allergic patients to fish muscle collagen

ABSTRACTBackground: In addition to parvalbumin, the well- known major allergen in fish, collagen was recently identified as a new allergen in the muscle of bigeye tuna and in the skin of several species of fish. The aim of the present study was to evaluate fish muscle colla- gens for their reactivity with IgE in fish-allergic patients and antigenic cross-reactivity.Methods: Collagen was purified from the white muscle of five species of fish (Japanese eel, alfonsin, mackerel, skipjack and bigeye tuna) by acid extraction and salt precipitation, whereas parvalbumin was purified from bigeye tuna by gel filtration and reverse- phase HPLC. The IgE reactivities to collagen and parvalbumin were examined by ELISA, whereas antigenic cross-reactivity among fish muscle collagens was investigated by ELISA inhibition experiments.Results: When 15 sera from fish-allergic patients were subjected to ELISA using bigeye tuna collagen and parvalbumin, 10 sera reacted only to parvalbumin, two reacted only to collagen, two reacted to both collagen and parvalbumin and one reacted to neither collagen nor parvalbumin. The sera containing specific IgE to bigeye tuna collagen also reacted to collagens from the other four species of fish. In the ELISA inhibition experiments, bigeye tuna collagen inhibited the binding of IgE not only to bigeye tuna collagen, but also to that from the other four species of fish, suggesting cross-reactivity among the collagens from five species of fish.Conclusions: These results demonstrate that some Japanese fish-allergic patients have specific IgE to fish muscle collagen and that fish muscle collagen is a cross-reactive allergen among various species of fish

Japanese Guideline for Childhood Asthma

The Japanese Guideline for the Diagnosis and Treatment of Allergic Diseases 2010 (JAGL 2010) describes childhood asthma based on the Japanese Pediatric Guideline for the Treatment and Management of Asthma 2008 (JPGL 2008) published by the Japanese Society of Pediatric Allergy and Clinical Immunology. JAGL 2010 provides information on diagnosis by age groups from infancy to puberty, treatment for acute exacerbations, long-term management by medication, daily life guidance, and patient education to allow physicians, not specialized in childhood asthma, to refer to this guideline for routine medical treatment. JAGL differs from the Global Initiative for Asthma Guideline (GINA) in that the former emphasizes long-term management of childhood asthma based on asthma severity and early diagnosis and intervention at <2 years and 2–5 years of age. However, a management method, including step-up or step-down of long-term management agents based on the status of asthma symptoms, is easy to understand and thus JAGL is suitable for routine medical treatment. JAGL also introduced treatment and management using a control test for children, recommending treatment and management aimed at complete control through avoiding exacerbation factors and appropriate use of antiinflammatory agents

A Study of the Usefulness of Anti-inflammatory Treatment for Mild Intermittent Asthma (Step 1): Budesonide vs. Montelukast

Background: Early intervention in adult asthma has been evaluated mostly with regard to symptoms, respiratory function and airway hyperresponsiveness, and has rarely been evaluated with regard to airway inflammation. Further, no clinical data concerning prevention of remodeling by anti-inflammatory therapy have been reported. The anti-inflammatory activities of an inhaled steroid and a leukotriene receptor antagonist were compared using sputum induced by inhaled hyperosmotic NaCl solution, and the usefulness of anti-inflammatory treatment for mild intermittent asthma (step 1) was investigated. Methods: The subjects of the study were patients with mild intermittent asthma (step 1) who had not received steroid treatment and had only been treated with inhaled β2-stimulants as needed. The subjects were divided into two groups : one group received 400 μg/day of budesonide (BUD group ; n = 15) and the other group received 10 mg/day of montelukast (MK group ; n = 12). The anti-inflammatory activities of BUD and MK were compared by examining respiratory function, exhaled nitric oxide (ENO) concentrations, airway hyperresponsiveness (acetylcholine provocation test) and the sputum induced by inhalation of hyperosmotic NaCl solution at three time points, i.e., before, 1 month after, and 6 months after the start of treatment. Results: It was shown that even in mild intermittent asthma (step 1) the levels of ENO and sputum eosinophil ratio were elevated, indicating that airway inflammation was clearly present and that airway hyperresponsiveness was elevated. The effects of BUD and MK in improving ENO and sputum eosinophil ratio were almost the same. However, airway hyperresponsiveness in both groups were not significantly improved after 1 and 6 months of treatment. Conclusions: Anti-inflammatory treatment is necessary even for mild intermittent asthma (step 1). We believe that early intervention with anti-inflammatory drugs is important for the prevention of airway remodeling, exacerbation of disease and progression to intractable asthma. Either of the two types of drugs, low-dose inhaled steroids or leukotriene receptor antagonists, can be selected as anti-inflammatory drugs for mild intermittent asthma