Kouichi Nishi

Comparison of atopic cough with cough variant asthma: is atopic cough a precursor of asthma?

Background: We have described a group of patients who present with isolated chronic bronchodilator resistant non-productive cough with an atopic constitution, eosinophilic tracheobronchitis, and airway cough receptor hypersensitivity without bronchial hyperresponsiveness, which we have termed “atopic cough”. Although cough variant asthma (in which the cough responds to bronchodilators) is recognised as a precursor of typical asthma, it is not known whether atopic cough is also a precursor of asthma. Methods: Eighty two patients with atopic cough were retrospectively examined for onset of typical asthma and compared with 55 patients with cough variant asthma (20 untreated patients and 35 treated with long term inhaled beclomethasone dipropionate (BDP), 218–467 μg/day). The median follow up period for patients with atopic cough and cough variant asthma was 4.8 (1–11.5) years and 3.7 (1–12.4) years, respectively. Results: Onset of typical asthma occurred in only one of the patients with atopic cough. In patients with cough variant asthma, typical asthma developed in two of 35 patients taking BDP and six of 20 untreated patients (difference 24.3%, 95% CI 2.8 to 45.8, p<0.02). Conclusions: These findings suggest that cough variant asthma is a precursor of typical asthma but that atopic cough is not. Treatment with inhaled steroids may prevent the transformation of cough variant asthma into typical asthma.

Importance of atopic cough, cough variant asthma and sinobronchial syndrome as causes of chronic cough in the Hokuriku area of Japan

Objective:  A prospective multicentre study was conducted to elucidate the causes of chronic cough in Japan.

Involvement of NK2 receptors rather than NK1 receptors in bronchial hyperresponsiveness induced by allergic reaction in guinea‐pigs

1 In this study, the role of neuropeptides in antigen‐induced bronchoconstriction and bronchial responsiveness in guinea‐pigs was evaluated by use of phosphoramidon, the inhibitor of neutral endopeptidases (NEP), the NK1 receptor antagonist, FK888, and the dual NK1/NK2 receptor antagonist, FK224. The role of endogenous tachykinins in bronchial hyperresponsiveness induced by inhaled capsaicin was also observed with FK888 and FK224. 2 Allergic bronchoconstriction and bronchial responsiveness was evoked by inhalation of ovalbumin (OA), and increasing doses of methacholine were inhaled at 5‐min intervals for 30 min after OA challenge in passively sensitized and artificially ventilated guinea‐pigs. Animals were treated with a 30 s inhalation of phosphoramidon (10−3m) or saline 10 min before the OA challenge. FK888 (1.0 or 10 mg kg−1) or FK224 (1.0 or 10 mg kg−1) was administered intravenously 5 min before the OA challenge. 3 Treatment with phosphoramidon did not alter the increase in the lateral pressure at the tracheal tube (Pao) caused by OA inhalation or the increase in bronchial response to methacholine following the allergic reaction. Pretreatment with FK224 did not inhibit the increase in Pao after antigen provocation but did significantly inhibit antigen‐induced bronchial hyperresponsiveness in a dose‐dependent manner, while FK888 did not affect either allergic bronchoconstriction or post‐allergic bronchial hyperresponsiveness. 4 Histamine, 25, 50, 100 or 200 μ ml−1 was inhaled for 20 s at 5‐min intervals in non‐sensitized guinea‐pigs which were pretreated with inhalation of subthreshold dose of capsaicin (10−7 m). FK888 or FK224, each at a dose of 0.1 or 1.0 mg kg−1, or vehicle was given to guinea‐pigs intravenously 3 min before inhalation of capsaicin. The capsaicin inhalation significantly potentiated bronchial responsiveness to histamine, compared with control. The capsaicin‐induced bronchial hyperresponsiveness was completely blocked by FK224 in a dose‐dependent manner but not by FK888. 5 These results suggest that NK2 receptors rather than NK1 receptors may play an important role in bronchial hyperresponsiveness induced by antigen challenge as well as capsaicin while tachykinins do not play a primary role in the acute bronchospasm elicited by antigen challenge in passively sensitized guinea‐pigs.

Effect of ethanol on airway caliber and nonspecific bronchial responsiveness in patients with alcohol-induced asthma.

No study has investigated the effects of ethanol on bronchial responsiveness in patients with alcohol‐induced asthma, although acetaldehyde, which is a metabolite of ethanol and is thought to be a main factor in alcohol‐induced asthma, causes both bronchoconstriction and bronchial hyperresponsiveness. The purpose of this study was to investigate the direct action of ethanol on the airway in patients with alcohol‐induced asthma. First, we investigated the bronchial response to inhalation of ascending doses (5, 10, and 20%) of ethanol in nine patients with alcohol‐induced asthma. Then, the bronchial responsiveness to methacholine was measured in 14 patients who were pretreated with saline or 20% ethanol in a double‐blind, randomized, placebo‐controlled, crossover fashion. Ascending doses of inhaled ethanol caused no significant changes in FEV1. The methacholine concentrations producing a 20% fall in FEV1 (PC20‐MCh) after 20%) ethanol (0.769 mg/ml, GSEM 1.514) were significantly (P= 0.0357) higher than those after saline (0.493 mg/ml, GSEM 1.368). This indicates that ethanol has a reducing effect on nonspecific bronchial responsiveness in patients with alcohol‐induced asthma; this paper is the first report on the effects of ethanol on bronchial responsiveness.

INHIBITORY EFFECT OF INHALED PROCATEROL ON ANAPHYLACTIC BRONCHOCONSTRICTION AND THROMBOXANE A2 PRODUCTION IN GUINEA-PIGS

This study was designed to examine whether an inhaled β2‐agonist, procaterol, inhibits thromboxane A2 (TXA2) production induced by antigen challenge in passively sensitized guinea‐pigs in vivo. Antigen‐induced bronchoconstriction was markedly inhibited by pre‐treatment with procaterol. Inhaled procaterol significantly reduced in a dose‐dependent manner the increment in TXB2 concentration in bronchoalveolar lavage fluid obtained 5 min after antigen challenge. Aerosol administration of procaterol significantly inhibited bronchoconstriction induced by inhaled hislainine. These results suggest that inhalation of procalerol has an inhibitory effect on antigen‐induced TXA2 production as well as a protective effect against bronchoconstriction induced by bronchoactive agents.

Potentiating effect of inhaled acetaldehyde on bronchial responsiveness to methacholine in asthmatic subjects.

BACKGROUND--It has recently been reported that acetaldehyde induces bronchoconstriction indirectly via histamine release. However, no study has been performed to assess whether acetaldehyde worsens bronchial responsiveness in asthmatic subjects so this hypothesis was tested. METHODS--Methacholine provocation was performed on three occasions: (1) after pretreatment with oral placebo and inhaled saline (P-S day), (2) after placebo and inhaled acetaldehyde (P-A day), and (3) after a potent histamine H1 receptor antagonist terfenadine and acetaldehyde (T-A day) in a double blind, randomised, crossover fashion. Nine asthmatic subjects inhaled 0.8 mg/ml acetaldehyde or saline for four minutes. After each inhalation a methacholine provocation test was performed. RESULTS--Methacholine concentrations producing a 20% fall in FEV1 (PC20-MCh) on the P-A day (0.48 mg/ml, 95% CI 0.21 to 1.08) and T-A day (0.41 mg/ml, 95% CI 0.22 to 0.77) were lower than those on the P-S day (0.85 mg/ml, 95% CI 0.47 to 1.54). There was no change in the PC20-MCh between the P-A and T-A days. A correlation was observed between the logarithmic values of PC20-MCh (log PC20-MCh) on the P-S day and the potentiating effect of acetaldehyde on the methacholine responsiveness [(log PC20-MCh on P-A day)-(log PC20-MCh on P-S day)] (rho = 0.82). CONCLUSIONS--Acetaldehyde induces bronchial hyperresponsiveness in patients with asthma by mechanisms other than histamine release.

A case of hypersensitivity pneumonitis caused by Humicola fuscoatra

A 51‐year‐old housewife with hypersensitivity pneumonitis caused by Humicola fuscoatra is reported. The diagnosis was made by an inhalation challenge with H. fuscoatra antigen. She was admitted for diagnosis and treatment of a fever and productive cough. Auscultation of her lungs revealed inspiratory fine crackles. Her chest CT showed diffuse miliary nodules in a centri‐lobular distribution with patchy ground glass opacities. Findings of transbronchial lung biopsy and BAL fluid were compatible with a hypersensitivity pneumonitis. Her symptoms worsened on returning home, which suggested the existence of some aetiological agent in the subjects house. H. fuscoatra, Penicillium decumbens and Aspergillus versicolor were isolated from a number of rooms. High titres of serum anti H. fuscoatra, P. decumbens and A. versicolor were detected. Inhalation challenge tests with both P. decumbens and A. versicolor antigen were negative, in contrast to that with H. fuscoatra which was positive. Based on these results, we advised the patient to cleanse her entire house. Since cleaning, her symptoms have not worsened upon returning home. This is the first report of hypersensitivity pneumonitis caused by H. fuscoatra antigen.

Comparison of the bronchodilator activities of oxitropium bromide, fenoterol, and their combination in patients with chronic obstructive pulmonary disease and bronchial asthma

The effects of an antimuscarinic agent, oxitropium bromide (200 µg), a beta-2 adrenoceptor agonist, fenoterol (200 µg), and their combination, were compared in ten patients with chronic obstructive pulmonary disease and ten patients with bronchial asthma, in a placebocontrolled, single blind crossover trial. In patients with chronic obstructive pulmonary disease, oxitropium and fenoterol produced a significant and similar degree of bronchodilatation. The duration of the bronchodilator effect was 3 h after oxitropium and 4 h after fenoterol, respectively. The combination of oxitropium and fenoterol produced a significantly greater degree of bronchodilatation than either drug alone. The duration of bronchodilatation in combination was 7 h and was considerably longer than that of each drug alone. In patients with bronchial asthma, oxitropium and fenoterol also caused bronchodilatation. Their combination produced a significantly greater degree of bronchodilatation than when either drug was used. The duration of the bronchodilator effects were 5 h after oxitropium, 4 h after fenoterol and 5 h after the combination. We conclude that the combination of oxitropium and fenoterol causes greater bronchodilatation in patients with chronic obstructive pulmonary disease and bronchial asthma than when compared to each drug alone. In the former, the duration of bronchodilatation is additionally prolonged. These combination effects may be of value in the clinical management of these common respiratory disorders.

Chronic eosinophilic pneumonia with endobronchial involvement.

We report here a case of chronic eosinophilic pneumonia with significant endobronchial involvement. A 59-year-old man was admitted complaining of fever, productive cough, wheezing, and dyspnea. There were ground-glass opacities in bilateral upper fields and tram track shadows in the left lower lung field on chest x-ray, and ground-glass opacities in bilateral upper lobes, thickening of the bronchial walls, and centrilobular nodules on computed tomographic scan of the chest. There was marked eosinophilia in the peripheral blood and bronchoalveolar lavage fluid and was diagnosed as chronic eosinophilic pneumonia. Bronchoscopy also revealed white nodules at the orifice of the right S and the left S bronchi. The histologic examination of these nodules revealed eosinophilic inflammation into the bronchial wall. This is a rare case of chronic eosinophilic pneumonia with endobronchial eosinophilic involvement.

Comparison of bronchoalveolar lavage cell findings in complete-resolution pneumonia and delayed-resolution pneumonia.

BACKGROUND In some patients with bacterial pneumonia, the resolution of chest radiograph shadows are delayed. There have been many clinical and pathological studies on delayed-resolution pneumonia (DR). However, there are no reports concerning inflammatory cell findings of bronchoalveolar lavage (BAL) fluid in patients with DR. We compared the BAL fluid cell findings in patients with DR with those in patients with complete-resolution pneumonia (CR). METHODS The subjects included six patients whose chest radiograph shadows were completely resolved within 2 weeks after an appropriate antibiotic administration (CR), and nine patients whose chest radiograph shadows were unresolved more than 2 weeks after the treatment (DR). BAL was done 2-3 weeks after the antibiotic treatment in both groups. We compared differential counts and lymphocyte subsets in BAL fluid among patients with CR, patients with DR, and asymptomatic subjects. RESULTS There were no significant differences in BAL fluid cell findings between CR groups and asymptomatic groups. On the other hand, the percentages of lymphocytes, neutrophils and eosinophils in DR group were significantly increased compared with those in CR and normal groups. There was no significant difference in the CD4+/CD8+ ratio of BAL lymphocytes among the three groups. CONCLUSIONS It is suggested that infiltration of inflammatory cells in the lung exists in DR, despite the disappearance of inflammatory reaction in the peripheral blood.