Lemierre syndrome complicated by bronchopleural fistula.

We present a 19-year-old woman, a case of Lemierre syndrome, who presented with fever, sore throat, and left shoulder pain. Imaging revealed a thrombus in the right internal jugular vein, multiple nodular shadows below both pleura with some cavitations, right lung necrotizing pneumonia, pyothorax, abscess in the infraspinatus muscle, and multiloculated fluid collections in the left hip joint. After inserting a chest tube and administering urokinase for the pyothorax, a bronchopleural fistula was suspected. The fistula was identified based on clinical symptoms and computed tomography scan findings. If a bronchopleural fistula is present, thoracic lavage should not be performed as it may cause complications such as contralateral pneumonia due to reflux.

Aspergillus fumigatus regulates mite allergen-pulsed dendritic cells in the development of asthma.

BACKGROUND: The role in allergic asthma development of the immune response against fungi with concomitant exposure to other common aeroallergens has yet to be determined. In particular, there is little understanding of how inhaled fungi affect the host response to mite allergens. OBJECTIVE: To characterize the in vitro and in vivo effects of concurrent exposure of Aspergillus fumigatus (Af) and Dermatophagoides farinae (Derf) on dendritic cells (DCs) in the development of allergic asthma. METHODS: Murine bone marrow-derived DCs were pulsed with Derf and/or live or heat-inactivated Af. Cytokine production and the expression of pathogen recognition receptors (PRRs) were determined in vitro. Subsequently, these DCs were inoculated into the airway of naïve mice to assess the development of allergic airway inflammation in vivo. The effect of antibodies against PRRs was also evaluated. RESULTS: Live Af significantly enhanced IL-10 production and the expression of Toll-like receptor (TLR) 2 and Dectin-1 in Derf-pulsed DCs. Live Af infection significantly attenuated Derf-pulsed DC-induced allergic airway inflammation in vivo. Antibodies against either TLR2 or Dectin-1 significantly reversed the inhibitory effects of live Af in the development of Derf-pulsed DC-induced allergic airway inflammation. CONCLUSION: Concurrent exposure of DCs to fungal antigens has profound influences on the subsequent mite allergen-induced allergic airway inflammation. Live Af could regulate the functions of airway DCs in the development of mite allergen-induced allergic airway inflammation via regulation of their PRRs. Our results suggest that concurrent exposure to pathogens such as fungi and mite allergens has profound influences on the subsequent allergen-induced allergic airway inflammation. Furthermore, modulating PRR signalling could provide a therapeutic regimen for the development of asthma.

Prevalence of chronic obstructive pulmonary diseases in general clinics in terms of FEV1/FVC.

BACKGROUND: The prevalence of chronic obstructive pulmonary disease (COPD) continues to increase all over the world. Nonetheless, COPD is often misdiagnosed in general clinics because of insufficient use of spirometry. OBJECTIVES: To estimate the prevalence of COPD in general clinics in Japan, we performed spirometry to screen patients who consulted general clinics. METHODS: Patients 40 years of age and older who consulted clinics in Nagasaki Prefecture, Japan, for non-respiratory diseases and who met certain inclusion criteria had their airflow limitation measured by spirometry. We defined COPD as forced expiratory volume in the first second (FEV(1)) over forced vital capacity (FVC) (FEV(1)/FVC) of < 70% in patients without active pulmonary disease, including physician-diagnosed asthma. RESULTS: Of the 1424 patients included in the study, 193 (13.6%) showed airflow limitation. Airflow limitation was significantly related to older age, male gender and cumulative pack-years. FEV(1)/FVC in patients with hypertension and chronic hepatitis were significantly lower than in patients without these diseases when adjusted for age, gender and pack-years. CONCLUSIONS: We showed that there are potentially a number of cases with COPD that are undiagnosed by general physicians in Japan. Measuring airflow limitation by spirometry in smokers with coexisting diseases, such as hypertension and chronic hepatitis, may be very beneficial because COPD is thought to be a systemic disease. The distribution of spirometers to general clinics is definitely needed to detect undiagnosed COPD.

Effects of various anti-asthmatic agents on mite allergen-pulsed murine bone marrow-derived dendritic cells.

BACKGROUND: Dendritic cells (DCs) play an important role in the immune response and are critically involved in asthma. beta2-agonists could potentially exacerbate type 2 T helper (Th2) cell-mediated immune response. OBJECTIVES: To determine the effects of various anti-asthmatic agents on DCs function both in vitro and in vivo. METHODS: Murine bone marrow-derived DCs were pulsed with mite allergen in the presence of pranlukast, salbutamol, salmeterol or fluticasone. These DCs were then inoculated intranasally into naïve mice to induce allergic airway inflammation in vivo. RESULTS: Pranlukast reduced IL-10 and increased IL-12, while fluticasone reduced both IL-10 and IL-12 production by mite allergen-pulsed DCs. Allergic airway inflammation in pranlukast- and fluticasone-treated and mite allergen pulsed DCs-harbouring mice was attenuated and such response was associated with inhibition of Th2 response in the airway. Salbutamol did not alter cytokine production, while salmeterol reduced IL-12 production by mite allergen-pulsed DCs. Lung pathology in beta2-agonist-harbouring mice was comparable with those of mite allergen-pulsed DCs-harbouring mice. CONCLUSIONS: Our results indicate that leukotriene receptor antagonists and corticosteroids inhibit DCs-induced Th2 skewed immune response, and that short- and long-acting beta2-agonists do not modify DCs-induced allergic airway inflammation.

Effects of primary and secondary low-grade respiratory syncytial virus infections in a murine model of asthma.

BACKGROUND: Respiratory syncytial virus (RSV) infection is known to develop and exacerbate asthma in young children. In adult, RSV causes recurrent but asymptomatic infections. However, the impact of asymptomatic RSV infection on adult asthma is yet to be determined. The present study is designed to determine the effects of primary and secondary low-grade RSV infections on allergic airway inflammation in a murine model of allergic asthma. METHODS: A low-grade RSV (2 x 10(3) plaque-forming units/mouse) was inoculated, and this caused neither pulmonary inflammation nor symptoms but induced significant IFN-gamma production in thoracic lymph nodes. To investigate interaction between low-grade virus and Dermatophagoides farinae (Df), airway hyper-responsiveness, lung inflammation and cytokine production from thoracic lymph nodes were compared after primary and secondary low-grade RSV infections in four groups of mice; control, Df allergen-sensitized, RSV-infected and Df-sensitized RSV-infected mice. A direct comparison between low- and high-grade RSV infections was also performed in primary infection. To investigate the role of IL-5 during secondary RSV infection, anti-IL-5 monoclonal antibody (anti-IL-5 mAb) was injected in mice and similar parameters were compared in four groups of mice. RESULTS: Primary high-grade RSV infection increased allergen-induced airway inflammation, while primary low-grade RSV infection attenuated allergen-induced airway inflammation concomitant with significant IFN-gamma production in lung-draining lymph nodes. In marked contrast, secondary low-grade RSV infection increased both IFN-gamma and IL-5 production, resulting in exacerbation of allergen-induced airway inflammation. Anti-IL-5 mAb treatment in secondary low-grade RSV infection and Df allergen-sensitized mice attenuated virus and allergen-induced airway inflammation. CONCLUSIONS: Low-grade RSV infection per se does not cause pulmonary inflammation, whereas it induces a significant immunological response in the allergen-sensitized host. These results indicate that subclinical and recurrent RSV infection may play an important role in exacerbation and maintenance of asthma in adults, wherein IL-5 is critically involved.

Pranlukast, a cysteinyl leukotriene receptor 1 antagonist, attenuates allergen-specific tumour necrosis factor alpha production and nuclear factor kappa B nuclear translocation in peripheral blood monocytes from atopic asthmatics.

BACKGROUND: The cysteinyl leukotriene receptor 1 (cysLTR1) antagonists are useful for oral treatment of bronchial asthma. The underlying mechanism of cysLTR1 antagonists on inhibition of inflammatory cytokine production is yet to be determined. OBJECTIVE: The present study was designed to determine the effect of pranlukast, a cysLTR1 antagonist, on production of inflammatory cytokines by allergen-stimulated peripheral blood monocytes (PBM) from atopic asthmatics. METHODS: PBM were obtained from normal control (n = 10) and Dermatophagoides farinae (Der f) allergen-sensitized atopic asthmatics (n = 12), and were cultured in the presence of Der f allergen. The production of TNF-alpha and nuclear-translocation of nuclear factor kappa B (NF-kappa B) was determined. In atopic asthmatics, pranlukast, tacrolimus or dexamethasone was added before stimulation by Der f. The additive effect of pranlukast and dexamethasone was also determined. RESULTS: PBM from atopic asthmatics cultured with Der f exhibited a significant increase in TNF-alpha production and nuclear translocation of NF-kappa B compared with normal control (P < 0.01). Pranlukast, tacrolimus and dexamethasone significantly inhibited production of TNF-alpha and nuclear-translocation of NF-kappa B in PBM of atopic asthmatics (P < 0.01). An additive effect of pranlukast on low-dose dexamethasone was also demonstrated. However, LTD4 did not induce TNF-alpha production or NF-kappa B nuclear translocation. CONCLUSION: Our results suggest that pranlukast may inhibit TNF-alpha production via suppression of NF-kappa B activation through pathways distinct from cysLTR1 antagonism.

Bronchial hyperresponsiveness and airway inflammation in adolescents with asymptomatic childhood asthma.

BACKGROUND: About 70% of childhood asthmatics become free of asthma-related symptoms during adolescence. Little is known about bronchial hyperresponsiveness (BHR) and airway inflammation in young adults with "outgrown" childhood asthma. METHODS: We studied 61 nonsmoking medical students (18 intermittent mild asthmatics, 23 students with outgrown childhood asthma but free of asthma-related symptoms for 10 years (asymptomatic asthmatics) and 20 healthy students). BHR and lung function were measured, and induced sputum samples analyzed for eosinophil count, eosinophilic cationic protein (ECP), granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha). RESULTS: BHR was still present in most asymptomatic asthmatics, but it was milder compared with healthy students. Only three subjects with previous asthma had no BHR and no signs of airway inflammation. Percentages of eosinophil, and ECP, TNF-alpha and GM-CSF concentrations in induced sputum of mild asthmatics and asymptomatic asthma groups were higher than in the healthy group. In asymptomatic asthmatics group, the duration of asthma, sputum eosinophil percentage, and the level of TNF-alpha in sputum correlated significantly with BHR. CONCLUSIONS: Only a few subjects with longstanding asymptomatic asthma could be considered as cured; most asymptomatic asthmatics continued to exhibit BHR and signs of airway inflammation. The outcome of childhood asthma and BHR was associated with the degree of airway inflammation and the duration of childhood asthma.

Airway hyperresponsiveness and pulmonary function in adult asthma.

BACKGROUND: Airway hyperresponsiveness (AHR) is a very important factor in the pathogenesis of bronchial asthma. OBJECTIVES: To examine the relationship between airway obstruction and AHR in adult asthma. METHODS: This study was a retrospective study in 161 adult asthmatic patients. Nonspecific AHR to methacholine was measured. We examined the correlations between AHR and pulmonary function, severity of asthma, type of asthma and age. RESULTS: In the moderate and severe groups, peripheral airway obstruction was more aggravated compared to the mild group, and AHR was significantly more severe. Analysis of AHR by age showed that the degree of airway obstruction increased with aging, but age did not clearly correlate with airway sensitivity. Airway reactivity decreased with aging. Aspirin-induced asthma tended to be severe. In fatal asthma, central airway obstruction was significantly more severe. Although AHR in fatal asthma did not significantly differ from that in the severe group, airway sensitivity and airway reactivity tended to be increased. CONCLUSIONS: AHR is an important factor determining the severity of asthma, and airway obstruction is an important index for the prediction of death from asthma. An evaluation of the degree of AHR and airway obstruction is considered to be the first step in controlling asthma.

Effects of amphotericin B gargles on oral colonization of Candida albicans in asthmatic patients on steroid inhalation therapy.

BACKGROUND: Early use of inhaled steroids is recommended for bronchial asthma. The side effects are rare, but oral discomfort and candidiasis are clinically important complications. Most previous studies reported that the use of spacer and water gargling was necessary to prevent oral complications. However, in some patients, this may fail to prevent such complications. OBJECTIVE: To compare the effects of water gargling with those of amphotericin B, in the prevention of oral complications in asthmatics using inhaled steroids. METHODS: Pharyngeal swab samples were obtained aseptically from the posterior pharyngeal wall of 128 asthmatics who have been using inhaled steroids (beclomethasone dipropionate) for more than 1 year. The amount of Candida albicans in cultured swabs was evaluated based on the following criteria: oral symptoms, method of gargling, dose of inhaled steroids, type of spacer and serum cortisol level. RESULTS: The number of isolated C. albicans was significantly higher in asthmatics with oral symptoms than in those free of symptoms. It was also significantly higher in patients who gargled with water or 1,000 times dilution than in those who gargled with 100 or 50 times dilutions of amphotericin B. Moreover, it was significantly higher in patients with low levels of serum cortisol than in those with normal serum cortisol. CONCLUSION: We demonstrated that at least in a subgroup of asthmatics using steroid inhalers, gargling with water or even weak concentrations of amphotericin B does not prevent colonization of the throat with C. albicans. This group at high risk of developing oral candidiasis should gargle with amphotericin B at concentrations higher than 100 times dilution that can prevent clinically detectable oral candidiasis.

Screening for acetaldehyde dehydrogenase 2 genotype in alcohol-induced asthma by using the ethanol patch test.

BACKGROUND: We have previously reported that alcohol-induced asthma in Japanese patients is caused by increased blood acetaldehyde concentration resulting from abnormalities of acetaldehyde dehydrogenase 2 (ALDH2) enzyme activity on the basis of ALDH2 genotype differences. OBJECTIVES: The purpose of the present study was to determine whether the ethanol patch test could predict the ALDH2 genotype in Japanese asthmatic subjects. METHODS: An ethanol patch test on the upper arm and a questionnaire survey addressing the past history of alcohol-induced asthma were administered to 148 adult Japanese asthmatic subjects. The ALDH2 genotypes in these 148 subjects were also determined by means of PCR. RESULTS: The genotype distribution of ALDH2 determined by PCR in 68 subjects with positive ethanol patch test results was 4 (5.9%), 56 (82.4%), and 8 (11.8%) for genotypes NN (normal homozygote), NM (mutant heterozygote), and MM (mutant homozygote). The ALDH2 genotype in 80 subjects with a negative test result was only NN. The distribution of ALDH2 genotype in 78 (52.7%) subjects who had experienced alcohol-induced asthma symptoms on the basis of the questionnaire was 27 (34.6%), 44 (56.4%), and 7 (9.0%) for genotypes NN, NM, and MM, respectively. On the other hand, 70 subjects had never experienced alcohol-induced asthma symptoms. In these subjects the ALDH2 genotype was NN in 51 (72.9%), NM in 18 (25.7%), and MM in 1 (1.4%). CONCLUSIONS: Our results indicate that the results of ethanol patch testing correlate well with ALDH2 genotype, as determined by means of PCR, suggesting that the ethanol patch test is useful for the screening of alcohol-induced asthma.

Preoperative steroid therapy inhibits cytokine production in the lung parenchyma in asthmatic patients.

OBJECTIVES: During or after surgery, asthma attacks due to airway hyperresponsiveness (AHR) are likely to occur in patients with bronchial asthma. Preoperative administration of corticosteroid for prevention of perioperative asthma attacks is useful. We examined the mechanism of prevention of perioperative asthma attacks by the preoperative administration of corticosteroid in vitro. DESIGN: Five patients with asthma were treated with 20 mg of prednisolone orally for 2 preoperative days and 80 mg of methylprednisolone IV immediately before and after surgery. In another five patients without asthma, no steroids were administered. A noncarcinomatous part of the resected tissue from each patient with lung cancer was passively sensitized with the serum of an atopic patient. In the patients without asthma, the tissue was treated with or without dexamethasone, and then mite antigen was added. MEASUREMENTS: The culture supernatant and lung tissue were recovered, and the supernatant was assayed for histamine, leukotriene E(4) (LTE(4)), interleukin (IL)-5, and tumor necrosis factor (TNF)-alpha. Degranulation of mast cells was measured by tryptase staining of the lung tissue, and the expression of messenger RNA (mRNA) of IL-5 and TNF-alpha was determined by the reverse transcriptase-polymerase chain reaction method. RESULTS: While preoperative administration of corticosteroid did not suppress the release of histamine and LTE(4) from the lungs of asthmatic patients, it completely suppressed IL-5 and TNF-alpha production at the mRNA level. The same results were obtained in lung tissues of nonasthmatic patients treated in vitro with dexamethasone. CONCLUSIONS: Our results suggest that corticosteroid treatment reduces AHR and prevents perioperative attacks of asthma primarily by suppressing the production of inflammatory cytokines.

Effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, combined with inhaled beclomethasone in patients with moderate or severe asthma.

BACKGROUND: Although inhaled steroids are used as the first line of therapy in asthmatic patients, symptoms of asthma do not improve completely in some patients. OBJECTIVE: To investigate the effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, in patients with moderate/severe asthma, when combined with beclomethasone dipropionate (BDP). METHODS: Protocol 1: After a 2-week observation period, 41 patients with moderate asthma were divided into those receiving BDP at 1,600 microg/day or 800 microg/day + pranlukast (450 mg/day). The effect of treatment was evaluated by measuring AM peak expiratory flow rate, symptom score, frequency of beta2-agonists, and daily variability of peak expiratory flow rate. Protocol 2: 39 patients participated in this study including those with moderate asthma on 800 microg/day BDP (group I), severe asthma on BDP at 1,600 microg/day (group II), and severe asthma on 1,600 microg/day BDP + 5 to 20 mg prednisolone (group III). Patients of all groups were additionally treated with pranlukast. RESULTS: Protocol 1: Both treatment regimens resulted in improvement in each clinical parameter. There were no significant differences in the effects of two treatment regimens. Protocol 2: Pranlukast was effective in group I and II, but not in group III. In groups I and II, pranlukast tended to be more effective when BDP was introduced within the first year of onset of asthma. CONCLUSIONS: Pranlukast is effective for patients with moderate asthma and those patients with severe asthma who are not treated with oral steroids. Pranlukast is more effective in patients treated with BDP early after onset.

Efficacy and safety of long-term treatment of asthmatic patients with pranlukast, a cysteinyl-leukotriene-receptor antagonist: four-year followup study.

BACKGROUND: There are few studies that have examined the long-term efficacy and safety of pranlukast, a leukotriene receptor antagonist, in asthmatic patients. METHODS: Sixty-three asthmatic patients were entered in this 4-year study [group 1, mild or moderate (N = 22); group 2, severe without using oral prednisolone (N = 22); group 3, severe with using oral prednisolone (N = 19)]. Pranlukast was administered at 225 mg twice daily to 14 subjects in group 1 (group 1p), 14 in group 2 (group 2p), and 11 in group 3 (group 3p), chosen for pranlukast additional therapy at random. Another group of 24 asthmatic patients was assigned to conventional therapy group (groups 1c, 2c, and 3c). Efficacy was determined by improvement in symptom score, peak expiratory flow rate (PEFR) percentage predicted, reduced daily variability of PEFR (percentage), and reduced frequency of use of rescue beta2-agonist (times per week). RESULTS: In groups 1p and 2p, PEFR percentage predicted began to improve from 2 weeks after commencement of treatment. The symptom score, daily variability of PEFR, and use of rescue beta2-agonist diminished significantly. In group 3p, pranlukast was ineffective in improving PEFR percentage predicted. All but two patients continued to receive pranlukast and no adverse effects were noted, at least during the 16-week therapy. Further, 22 patients continued to receive pranlukast for 4 years, and none experienced any adverse effects. CONCLUSIONS: We showed in this study that long-term treatment with pranlukast is effective for asthmatic patients without any adverse effects.

Effects of pranlukast on aspirin-induced bronchoconstriction: differences in chemical mediators between aspirin-intolerant and tolerant asthmatic patients.

BACKGROUND: Aspirin inhibits cyclooxygenase activity and modifies production of the arachidonate cascade in aspirin-induced asthma. The aim of the present study was to examine the effects of leukotriene (LT) receptor antagonist on aspirin challenge on eosinophil activity and chemical mediators released into the airway of asthmatic patients. METHODS: Aspirin oral provocation test was performed in aspirin-intolerant asthmatic patients (AIA; N = 7) and aspirin-tolerant asthmatic patients (ATA; N = 7). In AIA, LT receptor antagonist (pranlukast) was administered orally 2 hours before the test, and its inhibitory effects on sputum LTC4+C4, eosinophil cationic protein (ECP), eosinophil count, urinary LTE4/creatinine (Cr), 11-dehydrothromboxane (11-dhTX) B2/Cr, serum LTC4+D4, ECP, and peripheral blood eosinophil count were compared with the findings in ATA subjects. RESULTS: In AIA, aspirin induced an immediate reaction associated with increased urinary LTE4/Cr and sputum ECP and a fall in urinary 11-dhTXB2/Cr. Pranlukast inhibited the bronchial reaction and an increase in sputum ECP after threshold dosed of ASA, but failed to change aspirin-induced LT production in sputum and urine. In ATA, aspirin challenge was only associated with a fall in urinary 11-dhTXB2. CONCLUSIONS: Our results indicated that aspirin-induced asthma is associated with overproduction of LT with a shift to the 5-lipoxygenase series of the arachidonate cascade and that leukotriene receptor antagonist are useful for AIA through inhibition of production of LT and eosinophilic inflammation in the airway.

Tacrolimus inhibits cytokine production and chemical mediator release following antigen stimulation of passively sensitized human lung tissues.

BACKGROUND: The immunosuppressive effects of tacrolimus are mediated by inhibition of cytokine production by inflammatory cells. The role of tacrolimus on cytokine production and release of chemical mediators in asthma is not known at present. OBJECTIVES: We compared the effects of tacrolimus on interleukin (IL)-5 and tumor necrosis factor-alpha (TNF-alpha) production and chemical mediator release from excised human lung tissue with those of steroids. METHODS: Human lung tissue was passively sensitized with serum from atopic patients then preincubated with tacrolimus (10(-6), 10(-7), 10(-8) M) or dexamethasone (10(-6) M) for 2 hours. The lung tissue was then exposed to 1.5 microg/mL of mite antigen and then cultured for 48 hours. Culture supernatants were collected and IL-5 and TNF-alpha levels were measured by ELISA. IL-5 and TNF-alpha messenger ribonucleic acid (mRNA) expression was also investigated by reverse transcriptase-polymerase chain reaction. The level of histamine and leukotriene E4 was also measured in the culture supernatant. In addition, tryptase staining was performed to compare degranulation of mast cells. RESULTS: Antigen stimulation increased histamine and leukotriene release in the supernatant. Tacrolimus significantly and dose-dependently inhibited the release of histamine and leukotriene; dexamethasone did not. The results of tryptase staining demonstrated that tacrolimus dose-dependently inhibited degranulation of mast cells, whereas dexamethasone did not. Antigen stimulation increased TNF-alpha and IL-5 protein production and mRNA expression. Tacrolimus and dexamethasone significantly inhibited TNF-alpha and IL-5 protein production and mRNA expression. CONCLUSIONS: Our results indicated that tacrolimus is more powerful in inhibition of cytokine production and release of chemical mediators than steroids, and suggested that this immunosuppressor drug might be useful for the treatment of asthma.

Correlation between airway hyperresponsiveness and airway inflammation in a young adult population: eosinophil, ECP, and cytokine levels in induced sputum.

BACKGROUND: Eosinophil counts and eosinophil cationic protein (ECP) levels in the airway are elevated in asthmatic patients. However, few studies have examined the correlation between various cytokines in the sputum and airway hyperresponsiveness (AHR) in young adults with or without asthma. OBJECTIVE: We examined the correlation between AHR and eosinophil counts or ECP, and levels of several cytokines in the sputum. METHODS: We studied 120 nonsmoker students (group 1: intermittent mild asthmatic patients; group 2: subjects with history of childhood asthma; group 3: subjects sensitized by Dermatophagoides farinae with atopic disease; group 4: normal subjects sensitized by D. farinae; group 5: subjects with cedar pollinosis; and group 6: normal subjects). In each subject, AHR and lung function tests were measured, together with eosinophil count, ECP, granulocyte-macrophage colony-stimulating factor, TNF-alpha, IL-5, and interleukin-1beta in induced sputum. RESULTS: AHR in groups 1 and group 2 were high, in groups 5 and 6 low, and in groups 3 and 4 lower than in groups 1 and 2 but higher than groups 5 and 6. Percentages of eosinophils, ECP, and TNF-alpha in induced sputum in groups 1 and 2 were high, those in groups 5 and 6 were below detection limits, and those in groups 3 and 4 were lower than the percentages in groups 1 and 2. Granulocyte-macrophage colony-stimulating factor in the sputum was elevated only in group 1. The correlations between AHR and sputum eosinophil count, ECP, and TNF-alpha were significant, with the strongest correlation with TNF-alpha. CONCLUSIONS: Our results suggest that TNF-alpha levels in the sputum play an important role in determining the severity of AHR in young individuals. Further once AHR develops, it does not disappear, and the severity of airway inflammation influences the extent of AHR.

Airway foreign body with clinical features mimicking bronchial asthma.

A 56-year-old Japanese male with persistent cough, stridor and diffuse wheezing for 6 months had obstructive pulmonary dysfunction and airway hyperresponsiveness (AHR) to inhaled methacholine. Because of a poor response to glucocorticoid therapy and neutrophilia in the peripheral blood and sputum, chest computed tomography was performed and a plate-like tumor in the truncus intermedius was identified. Fiberoptic bronchoscopy demonstrated a plate-like green-colored tumor firmly impacted into the truncus intermedius and diffuse inflammatory changes spreading to both main bronchi. A piece of 'kombu' (Japanese kelp) was successfully removed by fiberoptic bronchoscopy under general anesthesia. Pulmonary function and methacholine inhalation tests became normal after the removal of the foreign body. In this case, it is suggested that asthma-like symptoms were due to localized airflow limitation in the right bronchus as well as to AHR associated with diffuse airway neutrophilic inflammation.

Blocking intercellular adhesion molecule-1 on human epithelial cells decreases respiratory syncytial virus infection.

The respiratory syncytial virus (RSV) causes potentially fatal lower respiratory tract infection in infants. The molecular mechanism of RSV infection is unknown. Our data show that RSV colocalizes with intercellular adhesion molecule-1 (ICAM-1) on the HEp-2 epithelial cell surface. Furthermore, a neutralizing anti-ICAM-1 mAb significantly inhibits RSV infection and infection-induced secretion of proinflammatory chemokine RANTES and mediator ET-1 in HEp-2 cells. Similar decrease in RSV infection is also observed in A549, a type-2 alveolar epithelial cell line, and NHBE, the normal human bronchial epithelial cell line when pretreated with anti-ICAM-1 mAb prior to RSV infection. Incubation of virus with soluble ICAM-1 also significantly decreases RSV infection of epithelial cells. Binding studies using ELISA indicate that RSV binds to ICAM-1, which can be inhibited by an antibody to the fusion F protein and also the recombinant F protein can bind to soluble ICAM-1, suggesting that RSV interaction with ICAM-1 involves the F protein. It is thus concluded that ICAM-1 facilitates RSV entry and infection of human epithelial cells by binding to its F protein, which is important to viral replication and infection and may lend itself as a therapeutic target.

[Clinical evaluation of 8 patients with pulmonary tuberculosis in a community hospital without restricted tuberculosis wards].

The clinical features of 8 patients with pulmonary tuberculosis under treatment in the Koebaru Central Hospital, a community hospital without restricted tuberculosis wards, between 1992 and 2000 were evaluated. The major findings in the present study were: i) recently, the number of elderly patients with reactivated pulmonary tuberculosis has increased, ii) none of the patients showed respiratory symptoms, and 3 patients had negative Mantoux skin tests, iii) only one patient showed cavities on chest radiography, and iv) none of the expectorated sputum samples was smear-positive for Mycobacterium tuberculosis. Smears of intrabronchial sputum sampled using a fiberoptic bronchoscope from pulmonary lesions in patients without any symptoms were useful for establishing the diagnoses. Considering all aspects, it is important to perform aggressive evaluations, even for elderly patients, utilizing a fiberoptic bronchoscope for early diagnosis of pulmonary tuberculosis and to prevent nosocomial infections.