Masayoshi Minakuchi

Airway remodelling in cough-variant asthma.

Subepithelial-layer thickening, a pathological feature of airway remodelling, is present in cough-variant asthma. In bronchial biopsy samples we found mean subepithelial-layer thickness was 7.1 (SE 0.4) microm in patients with cough-variant asthma, 8.6 (0.4) microm in patients with classic asthma with wheezing, and 5.0 (0.2) microm in healthy controls. Thickness was significantly higher in patients with asthma than in controls, and was significantly greater in those with classic asthma than in those with cough-variant asthma. Early anti-inflammatory treatment might, therefore, be beneficial in cough-variant asthma, as recommended in classic asthma.

Relationship of airway wall thickening to an imbalance between matrix metalloproteinase-9 and its inhibitor in asthma

Background: The balance between matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) may be critical in extracellular matrix remodelling, a characteristic of asthmatic airways. An excess of TIMP-1 over MMP-9 has been associated with chronic airflow obstruction but the mechanisms underlying this association remain unknown. Recent computed tomographic (CT) studies indicate that airway wall thickening is associated with chronic airflow obstruction. Methods: Sputum levels of MMP-9, TIMP-1, and their molar ratio were examined in 26 patients with stable asthma and their relationship with pulmonary function and airway wall thickness, assessed by a validated CT technique which measured wall area corrected by body surface area (WA/BSA), the ratio of WA to outer wall area (WA%), and the absolute wall thickness corrected by √BSA of a segmental bronchus (T/√BSA), was examined. Results: Sputum MMP-9 levels were inversely correlated with WA% and TIMP-1 levels were positively correlated with WA/BSA and T/√BSA. The MMP-9/TIMP-1 molar ratio was inversely correlated with WA% and T/√BSA and positively correlated with post-bronchodilator values of mid-forced expiratory flow and maximum expiratory flow at the quartile of lung volume. Conclusion: Excess TIMP-1 may have a pathogenetic role in airway wall thickening in asthmatic patients which may result in chronic airflow obstruction.

Chronic Eosinophilic Pneumonia: Treatment with Inhaled Corticosteroids

Background: Chronic eosinophilic pneumonia (CEP) is highly sensitive to systemic corticosteroids, but frequently relapses if the dose is tapered or treatment discontinued. Long-term usage of systemic corticosteroids may cause side effects. Alternative treatments are therefore desired. Objectives: We evaluated the response of CEP to monotherapy with inhaled corticosteroids (ICS). Methods: Four patients who had CEP without spontaneous resolution were studied. Patients received inhaled beclomethasone dipropionate (BDP) at a dose of 0.8 mg/day in 1 patient and 1.6 mg/day in 3 patients for 2 weeks. Treatment was continued if a patient showed improvement in at least 1 of the following indices: radiological findings, symptoms, and blood eosinophilia. Results: After the initial 2 weeks of treatment with BDP, the blood eosinophil count increased in 2 patients and decreased in 2. Symptoms worsened in 2 and improved in 2. Infiltrates on chest radiography increased in 3 and showed little change in 1. In the 2 patients with worsening of all 3 outcome indices, oral prednisolone was started; the indices improved. In the remaining 2 patients, BDP alone was continued. One patient had worsening of CEP after 2 months of treatment, and another had relapse of CEP at 3.5 years while receiving 1.6 mg/day of BDP. All patients thus finally had worsening or relapse of CEP during treatment with BDP. Conclusions: ICS may not be effective when given as monotherapy in patients with CEP.

Serum eosinophil cationic protein levels measured during exacerbation of asthma: characteristics of patients with low titres

Background Serum eosinophil cationic protein (ECP) levels reflect ongoing eosinophilic airway inflammation and are used as a marker for asthma activity. ECP levels, however, may not be elevated in some asthmatic patients, even when they are symptomatic.

Corticosteroid-induced myopathy mimicking therapy-resistant asthma

BACKGROUND Therapy-resistant asthma is an important clinical problem. However, before considering asthma truly therapy resistant, it is essential to exclude diagnoses that may masquerade as therapy-resistant asthma, such as vocal cord dysfunction and recurrent aspiration, as well as factors related to loss of asthma control, including poor compliance, exposure to allergens, and sinusitis. Corticosteroid-induced myopathy may be an unrecognized but potentially important consideration in both settings. OBJECTIVES To describe a patient with corticosteroid-induced myopathy complicating recurrent exacerbations of asthma, which presented with persistently reduced airflow that mimicked therapy-resistant asthma. METHODS A 20-year-old Japanese woman with severe intractable asthma who had a history of near-fatal attacks was admitted with recurrent asthma exacerbations that required long-term systemic corticosteroids. RESULTS Wheezing episodes decreased but airflow limitation persisted, which was due to not only uncontrolled asthma but also corticosteroid-induced myopathy. Myopathy prevented the adequate use of inhalers, which in turn complicated the tapering of corticosteroids, leading to a vicious cycle. Careful and gradual reduction of corticosteroid dose, while continuing systemic administration of nonsteroidal antiasthma medications, resulted in a resolution of clinical and electromyographic signs of myopathy and pulmonary function abnormalities. CONCLUSIONS Corticosteroid-induced myopathy can masquerade as therapy-resistant asthma and can cause poor asthma control.