Chest tightness is relieved with the use of asthma drugs except bronchodilators

Objective: Many patients with a chief complaint of chest tightness are examined in medical facilities, and a lack of diagnosis is not uncommon. We have reported that these patients often include those with chest tightness relieved with bronchodilator use (CTRB) and those with chest tightness relieved with the use of asthma drugs except bronchodilators (CTRAEB). The purpose of this study was to demonstrate the clinical characteristics of the patients with CTRAEB and compare them with data from patients with CTRB. Methods: Patients with CTRB (n?=?13) and CTRAEB (n?=?7) underwent a bronchodilator test, assessments of airway responsiveness to methacholine, bronchial biopsy, and bronchial lavage under fiberoptic bronchoscopy before receiving treatment. In all, 10 healthy subjects, 11 bronchial biopsy control patients, and 10 asthmatic patients were recruited for comparison. Results: Inhalation of a short-acting ß₂-agonist (SABA) increased the forced expiratory volume in one second (FEV₁) by 5.1%?±?4.0% in patients with CTRB and by 1.3%?±?3.5% in patients with CTRAEB, and the difference was statistically significant (p?=?0.0449). The bronchial biopsy specimens from the patients with CTRB and CTRAEB exhibited significant increases in T cells (p?<?.05) compared with those of the control subjects. The bronchial responsiveness to methacholine was increased in only a minor portion of patients with CTRB and CTRAEB. Conclusions: We hypothesized that the clinical condition of patients with CTRAEB involves chest tightness arising from inflammation alone, and this chest tightness is mostly associated with airway T cells, without constriction of the airways. There is little to distinguish CTRAEB from CTRB aside from the response to bronchodilator treatment.

This clinical trial is registered at www.umin.ac.jp (UMIN13994, 13998, and 16741).     

Chest Pain Relieved with a Bronchodilator or Other Asthma Drugs

BackgroundAlthough many patients who experience chest pain or pressure consult their physicians, unfortunately a large number of them do not, and consequently they remain undiagnosed and untreated. Chest pain, in a subset of these patients, may be relieved with a bronchodilator or other asthma drugs.MethodsThis retrospective study included twenty cases of chest pain that were relieved with asthma drugs. Chest pain was categorized into three types: chest pain variant asthma, bronchial asthma with chest pain, and non-asthmatic allergic chest pain. Chest pain variant asthma was defined as chest pressure that improved in response to a bronchodilator, without the characteristic attacks of bronchial asthma. Bronchial asthma with chest pain was defined as chest pressure, with the characteristic attacks of bronchial asthma that improved following the administration of a leukotriene receptor antagonist, systemic corticosteroid, or bronchodilator. Non-asthmatic allergic chest pain was defined as chest pressure without the typical asthma attack, but with chest pressure that improved in response to a leukotriene receptor antagonist or systemic corticosteroid, but not a bronchodilator.ResultsFourteen cases of chest pain were diagnosed as variant asthma, three cases were diagnosed as bronchial asthma with chest pain, and three cases were diagnosed as non-asthmatic allergic chest pain.ConclusionsThe results suggest that the mechanism underlying chest pain that is relieved with asthma drugs can involve either an airway constriction pathway or a non-constrictive pathway presumably airway inflammation. Analysis of the patient's response to treatment with asthma medication is useful for the correct diagnosis of the source of chest pain.     

Bronchoalveolar lavage does not alter airway responsiveness in asthmatic subjects

Bronchoalveolar lavage (BAL) during fiberoptic bronchoscopy is being used increasingly for the investigation of asthma. Airway responsiveness to methacholine is a sensitive indicator of the presence and severity of asthma. Therefore, we studied the effect of BAL on methacholine airway responsiveness in stable asthmatics. Geometric mean methacholine PC20 was 1.34 mg/ml before and 1.80 mg/ml after BAL (p = 0.26) in asthmatics. Immediate symptoms of airway narrowing after BAL occurred only in the 3 asthmatics with moderate to severe hyperresponsiveness. These symptoms were rapidly relieved by inhaled bronchodilator. There was no relationship between the occurrence of symptoms and the amount of topical lidocaine used for local anaesthesia or the volume of lavage fluid returned. The absence of an effect of BAL on airway responsiveness supports the safety of this procedure in the controlled asthmatic patient with near normal FEV1, irrespective of the level of baseline airway responsiveness.     

Association of airway pentosidine levels with bronchodilator response mediated by salbutamol administration in asthmatic patients

BackgroundRecently, increased levels of pentosidine, an intermolecular cross-linking type of advanced glycation end products, are observed in the airways of asthmatic patients. This study was designed to determine whether differences in bronchodilator response among individuals with asthma are attributable to pentosidine levels in their airways.MethodsFifty-six asthmatic patients (21 with airway obstruction, 35 without airway obstruction) and 10 normal controls were included in this study. For asthmatic patients, we evaluated the spontaneous reversibility of airway obstruction or the reversibility that can be obtained after methacholine provocation. And we also measured pentosidine levels and percentage of sputum eosinophils in induced sputum, and exhaled nitric oxide (NO) levels.ResultsThe pentosidine levels did not significantly differ between the two asthmatic subgroups with and without airway obstruction. In asthmatic patients without airway obstruction, airway hyperresponsiveness to methacholine (PC20 methacholine) was significantly correlated with sputum eosinophils and exhaled NO levels. In contrast, PC20 methacholine was not significantly correlated with pentosidine levels. In asthmatic patients with or without airway obstruction, bronchodilator response was not significantly correlated with sputum eosinophils and exhaled NO levels. However, bronchodilator response was closely correlated with pentosidine levels (asthmatics without airway obstruction: r = ?0.54, p = 0.002; asthmatics with airway obstruction: r = ?0.48, p = 0.03).ConclusionsOur results showed that pentosidine might be a potential biomarker reflecting the reduced bronchodilator response in asthma. This study will provide new insights into the mechanisms underlying persistent airway obstruction.     

Chest pain variant asthma

We present the cases of three patients who initially presented with chest pain but were ultimately diagnosed as having asthma. None had audible wheezing. A diagnosis of asthma was entertained and ultimately supported by a clinical response to bronchodilator therapy. Only one patient had significant but intermittent documentable reversible airway obstruction, while another had marked sensitivity to methacholine bronchial challenge. Two patients required short courses of oral corticosteroids before symptom ablation.     

Airway Reactivity Is a Determinant of Bronchodilator Responsiveness After Methacholine‐induced Bronchoconstriction

Airway hyperresponsiveness (AHR) is one of the characteristics of asthma and a risk factor for persistent airflow limitation. Poor response to bronchodilator may be a cause of persistent airflow limitation. Multiple factors may determine bronchodilator responsiveness, including airway reactivity to nonspecific bronchoconstrictive agents. If patients with AHR have poor bronchodilator responsiveness, then it could be a potential mechanism for asthma and persistent airflow limitation in these patients. The objective of this study is to assess the relationship between airway reactivity to methacholine and responsiveness to beta‐agonist and beta‐agonist/anticholinergic combination in a large subject population. A retrospective data analysis was undertaken of 764 consecutive subjects with ≥ 20% reduction in forced expiratory volume during the first second of exhalation from total lung capacity (FEV1) after ≤ 189 cumulative units of methacholine. The first 382 subjects received 3 inhalations of metaproterenol and the second 382 subjects received 3 inhalations of albuterol and ipratropium combination after ≥ 20% reduction in FEV1. Bronchodilator responsiveness was measured as the percent increase in FEV1 after the treatment. Airway reactivity was assessed as the log10 of methacholine dose response slope. In a simple linear regression model, airway reactivity was significantly related to bronchodilator responsiveness. The coefficient of determination (r²) was 0.15 for the whole groups; 0.14 for metaproterenol group and 0.18 for albuterol/ipratropium combination group (all p < 0.0001). The regression coefficient (β) was 14.0 for the whole group; 14.8 and 13.2, respectively, for the two bronchodilator groups. Airway reactivity to methacholine is a determinant of airway responsiveness to both beta‐agonist and beta‐agonist/anticholinergic combination. Subjects with higher airway reactivity have higher bronchodilator responsiveness.     

Response of upper and lower airway inflammation to bronchial challenge with house dust mite in Chinese asthmatics: a pilot study

BackgroundAllergen nasal challenge can induce increase of eosinophils in sputum, but report about eosinophilic inflammation in upper airway after allergen bronchial challenge in Chinese asthmatics was rare. The article aims to evaluate response of upper and lower airways to house dust mite (HDM) allergen bronchial challenge.MethodsHDM allergen bronchial challenge was carried out in asthmatic patients with allergic rhinitis (AR). Bronchial methacholine challenge and blood test were performed before and at 24 hours after allergen challenge. Nasal lavage and induced sputum for differential cells count and fractional exhaled nitric oxide (FeNO) measurement were performed before, 7 and 24 hours after allergen challenge.ResultsEighteen asthmatic patients with AR underwent HDM allergen bronchial challenge with no serious adverse events reported. Fifteen patients showed dual asthmatic response (DAR), while 2 patients showed early (EAR) and 1 late asthmatic response (LAR) only. At 24 hours after allergen bronchial challenge testing, average PC₂₀FEV₁ to methacholine significantly decreased (1.58 to 0.81 mg/mL, P=0.03), while both FeNO and the percentage of eosinophils in blood and sputum were significantly increased [52.0 (54.0) to 69.0 (56.0) ppb, P=0.01; 4.82% to 6.91%, P<0.001; 20.70% to 27.86%, P=0.03, respectively], but with no significant differences found in the percentage of eosinophils in nasal lavage (39.36% to 38.58%, P=0.89). However, at 7 hours after allergen challenge, the eosinophils in sputum were significant increased to 40.45% (P<0.001), but there was an increase (39.36% to 48.07%) with no statistical difference (P=0.167) found in nasal lavage.ConclusionsHDM allergen bronchial challenge induced different response of airway inflammation in upper and lower airways.     

Sputum eosinophilia and bronchial responsiveness in patients with chronic non-productive cough responsive to anti-asthma therapy

OBJECTIVE: We aimed to examine airway inflammation and bronchial responsiveness in patients with chronic non-productive cough responsive to anti-asthma therapy. METHODOLOGY: Bronchial responsiveness to methacholine as well as the number of inflammatory cells and concentration of eosinophil cationic protein (ECP) in induced sputum were measured in 42 patients with chronic non-productive cough of unknown origin. Their response to bronchodilator, antiallergic and inhaled or oral glucocorticoid therapy was subsequently assessed. RESULTS: Complete remission of coughing was attained with anti-asthma therapies in 34 patients (responder group), while eight patients did not respond (non-responder group). Twenty patients in the responder group and three in the non-responder group showed bronchial hyperresponsiveness (BHR). The number of eosinophils and ECP levels in the sputum from responders with BHR were significantly increased when compared with those from non-responders and healthy subjects. These sputum measures were also significantly increased in responders without BHR when compared with healthy subjects. However, there were no significant differences in these inflammatory markers between the responders with and without BHR. The neutrophil numbers in the sputum from non-responders and responders both with and without BHR were also significantly higher than in control subjects, but there were no significant differences. CONCLUSIONS: These findings suggest that patients with chronic non-productive cough responsive to anti-asthma therapy characteristically have eosinophilic airway inflammation, which may play an important role in the development of chronic cough. Furthermore, the evaluation of not only bronchial responsiveness but also airway inflammation by examination of induced sputum may be useful for diagnosis and deciding on therapeutic strategies.     

The effect of bronchoalveolar lavage on bronchial responsiveness in patients with airflow obstruction

This study assessed the effect of bronchoalveolar lavage (BAL) on nonspecific bronchial responsiveness in 31 patients. Of these, 20 had airflow obstruction; 11 control subjects had normal pulmonary function. Bronchial responsiveness to methacholine, expressed as the dose of inhaled methacholine required to provoke a 20 percent fall in forced expiratory volume in one second (PD20 FEV1), was measured before and after BAL. We found no evidence for the induction of responsiveness by BAL in 11 control subjects with negative methacholine tests prior to the procedure. There were small but significant falls in FEV1 following BAL in both the control group and in patients with airflow obstruction. Thus, BAL does not appear to induce nonspecific bronchial hyperresponsiveness in subjects without airflow obstruction, nor does it affect airway responsiveness in emphysema patients. Among asthmatics, bronchial responsiveness can be increased as a result of BAL; this increase was greatest in patients who were most responsive initially.     

支气管镜检对不明原因胸闷患者的诊断价值研究

目的利用电子支气管镜对不明原因胸闷患者进行检查。方法收集我院呼吸内科门诊不明原因胸闷患者78例,电子支气管镜检查,并行支气管刷检、活检、支气管肺泡灌洗液检查。结果支气管镜检查显示:支气管肺癌19例(24.4%),炎性改变17例(21.8%),支气管结核11例(14.1%),痰栓所致肺不张8例(10.3%),支气管异物6例(7.7%),支气管狭窄2例(2.6%),支气管正常改变15例(19.2%)。灌洗液发现可疑肿瘤细胞10例(12.8%),灌洗培养阳性12例(15.4%);黏膜刷检11人次发现抗酸杆菌(14.1%),发现可疑肿瘤细胞6例(7.7%);肿物活检:结核结节7例(9.0%),鳞癌14例(17.9%)腺癌5例(6.4%)。结论电子支气管镜检查及支气管黏膜刷检、肺泡灌洗液、活检,对不明原因胸闷患者病因诊断有重要意义。     

Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma

IgE plays an important role in allergic asthma. We hypothesized that reducing IgE in the airway mucosa would reduce airway inflammation. Forty-five patients with mild to moderate persistent asthma with sputum eosinophilia of 2% or more were treated with humanized monoclonal antibody against IgE (omalizumab) (n = 22) or placebo (n = 23) for 16 weeks. Outcomes included inflammatory cells in induced sputum and bronchial biopsies, and methacholine responsiveness. Treatment with omalizumab resulted in marked reduction of serum IgE and a reduction of IgE+ cells in the airway mucosa. The mean percentage sputum eosinophil count decreased significantly (p < 0.001) from 6.6 to 1.7% in the omalizumab group, a reduction significantly (p = 0.05) greater than with placebo (8.5 to 7.0%). This was associated with a significant reduction in tissue eosinophils; cells positive for the high-affinity Fc receptor for IgE; CD3+, CD4+, and CD8+ T lymphocytes; B lymphocytes; and cells staining for interleukin-4, but not with improvement in airway hyperresponsiveness to methacholine. This study shows antiinflammatory effects of omalizumab treatment and provides clues for mechanisms whereby omalizumab reduces asthma exacerbations and other asthma outcomes in more severe asthma. The lack of effect of omalizumab on methacholine responsiveness suggests that IgE or eosinophils may not be causally linked to airway hyperresponsiveness to methacholine in mild to moderate asthma.     

Airway reactivity is a determinant of bronchodilator responsiveness after methacholine-induced bronchoconstriction.

Airway hyperresponsiveness (AHR) is one of the characteristics of asthma and a risk factor for persistent airflow limitation. Poor response to bronchodilator may be a cause of persistent airflow limitation. Multiple factors may determine bronchodilator responsiveness, including airway reactivity to nonspecific bronchoconstrictive agents. If patients with AHR have poor bronchodilator responsiveness, then it could be a potential mechanism for asthma and persistent airflow limitation in these patients. The objective of this study is to assess the relationship between airway reactivity to methacholine and responsiveness to beta-agonist and beta-agonist/anticholinergic combination in a large subject population. A retrospective data analysis was undertaken of 764 consecutive subjects with > or = 20% reduction in forced expiratory volume during the first second of exhalation from total lung capacity (FEV1) after < or = 189 cumulative units of methacholine. The first 382 subjects received 3 inhalations of metaproterenol and the second 382 subjects received 3 inhalations of albuterol and ipratropium combination after > or = 20% reduction in FEV1. Bronchodilator responsiveness was measured as the percent increase in FEV1 after the treatment. Airway reactivity was assessed as the log10 of methacholine dose response slope. In a simple linear regression model, airway reactivity was significantly related to bronchodilator responsiveness. The coefficient of determination (r2) was 0.15 for the whole groups; 0.14 for metaproterenol group and 0.18 for albuterol/ipratropium combination group (all p<0.0001). The regression coefficient (beta) was 14.0 for the whole group; 14.8 and 13.2, respectively, for the two bronchodilator groups. Airway reactivity to methacholine is a determinant of airway responsiveness to both beta-agonist and beta-agonist/anticholinergic combination. Subjects with higher airway reactivity have higher bronchodilator responsiveness.     

Protocol digest of randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer: Japan clinical oncology group study (JCOG1407)

Gemcitabine is one of the standard treatments for locally advanced pancreatic cancer. Recent studies on metastatic pancreatic cancer have shown that combination chemotherapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP) prolonged the overall survival compared with gemcitabine alone. To select the most promising chemotherapy, a randomized phase II selection design trial was started in July 2016 to compare between modified FOLFIRINOX and GnP for patients with locally advanced pancreatic cancer. A total of 124 patients will be enrolled from 36 Japanese institutions within 2.5 years. The primary endpoint is the proportion of 1-year overall survival, and secondary endpoints are progression-free survival, distant metastasis-free survival, response rate in patients with target lesions, CA19-9 response, adverse events, treatment-related death, early death, grade 4 non-hematological toxicity, and dose intensity. This trial has been registered with the UMIN Clinical Trials Registry [http://www.umin.ac.jp/ctr/index.htm], and the registration number is UMIN000023143.     

Chronic eosinophilic pneumonia complicated by bronchial asthma and diabetes mellitus successfully treated with suplatast tosilate and high-dose inhaled corticosteroid therapy]

A 54-year-old woman complained of dyspnea, cough, and productive sputum. Auscultation detected a wheeze in the left and right lung fields. Chest x-ray and computed tomographic films showed non-segmental infiltration in the left upper lung field. Laboratory data revealed eosinophilia in peripheral blood and sputum, elevated levels of serum interleukin-5 (IL-5), airflow limitation, hypoxemia, and heightened airway sensitivity to methacholine (D min : 0.42 units). Bronchoalveolar lavage disclosed an increase in the total number of cells, a 32% increase in eosinophils, and a decreased CD 4/CD 8 ratio of 0.7. Transbronchial lung biopsy specimens revealed infiltrations of eosinophils in the alveolar and interstitial compartments. The histologic features of bronchial biopsy specimens included increased eosinophils in the submucosa and squamous metaplasia. In addition, blood glucose and HbA 1 c levels were elevated. Chronic eosinophilic pneumonia complicated by bronchial asthma and diabetes mellitus was diagnosed. Because the patient was diabetic, she was given suplatast tosilate to reduce the production of IL-5, and high-dose inhaled corticosteroid (beclometasone dipropionate, 1,600 mcg/day) instead of oral corticosteroid therapy. Her symptoms were relieved, peak expiratory flow rates increased, serum IL-5 levels became undetectable, airway sensitivity to methacholine decreased (D min : 4.64 units), and the radiographic abnormalities disappeared. Furthermore, treatment with beclomethasone dipropionate was progressively reduced to 1,200 mcg/day over the subsequent year without relapse. It was concluded that suplatast tosilate and high-dose inhaled corticosteroid therapy may be an effective alternative therapeutic approach to chronic eosinophilic pneumonia in some cases.     

Bronchoalveolar cell profiles of asthmatic and nonasthmatic subjects

Asthma is associated with increased airway responsiveness to pharmacologic agents such as methacholine. Increases in airway responsiveness after exposure to allergen or ozone are associated with increased inflammatory cells in bronchoalveolar lavage both in human and in animal studies. We studied the total and differential cell counts in 10 stable atopic asthmatics who had airway hyperresponsiveness but no clinical features of airway inflammation and 10 nonasthmatic subjects, using a conventional 100-ml lavage and a 20-ml washing. Metachromatic cell numbers and eosinophils were increased in both the lavage (p less than 0.01 for metachromatic cells; p = 0.05 for eosinophils) and washing (p less than 0.025 for metachromatic cells and p = 0.03 for eosinophils) compared with those in nonasthmatics. In asthmatics, metachromatic cell numbers in the lavage and washing, and total cell count and, to a lesser extent, eosinophils in lavage were significantly correlated with measurements of airway responsiveness. Major basic protein in lavage and blood did not differ between asthmatics and nonasthmatics. The washing, although it revealed a different cell profile from the lavage in both normal subjects and asthmatics, did not show differences between asthmatics and nonasthmatics undetected by the lavage specimen. We conclude that there is evidence of cellular inflammation in the airway of stable asthmatics and that small volume washings do not add to the information concerning the cell profile of asthmatics and nonasthmatics provided by conventional lavage.     

Bronchial hyperresponsiveness in subjects with gastroesophageal reflux

BACKGROUND: The relationship between gastroesophageal reflux (GER) and asthma has been widely studied in the last years. GER may interfere with airway reactivity and aggravate or even induce asthma. OBJECTIVE: To assess the prevalence of bronchial hyperresponsiveness (BHR) in patients with GER disease with a view to judging the potential influence of GER on BHR. METHODS: 30 patients with GER disease and no clinical evidence of asthma and 30 normal subjects underwent a methacholine bronchial challenge. The methacholine concentration that caused a 20% fall in the FEV(1) (PC20) was used to assess bronchial responsiveness. RESULTS: In the GER group 11 subjects of the 30 studied showed a PC20 methacholine equal to or less than 8 mg/ml while in the control group only 2 subjects had a PC20 methacholine equal to or less than 8 mg/ml (p < 0.01; ANOVA test). CONCLUSIONS: Subjects with GER had a greater increase in airway reactivity when inhaling methacholine compared to disease-free normal subjects.     

Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease

To determine whether patients with fixed airflow obstruction have distinct pathologic and functional characteristics depending on a history of either asthma or chronic obstructive pulmonary disease (COPD), we characterized 46 consecutive outpatients presenting with fixed airflow obstruction by clinical history, pulmonary function tests, exhaled nitric oxide, sputum analysis, bronchoalveolar lavage, bronchial biopsy, and high-resolution computed tomography chest scans. Subjects with a history of COPD (n = 27) and subjects with a history of asthma (n = 19) had a similar degree of fixed airflow obstruction (FEV1: 56 +/- 2 versus 56 +/- 3% predicted) and airway hyperresponsiveness (PC20FEV1: 2.81 [3.1] versus 1.17 [3.3]). Subjects with a history of asthma had significantly more eosinophils in peripheral blood, sputum, bronchoalveolar lavage, and airway mucosa; fewer neutrophils in sputum and bronchoalveolar lavage fluid; a higher CD4+/CD8+ ratio of T cells infiltrating the airway mucosa; and a thicker reticular layer of the epithelial basement membrane. They also had significantly lower residual volume, higher diffusing capacity, higher exhaled nitric oxide, lower high-resolution computed tomography scan emphysema score, and greater reversibility to bronchodilator and steroids. In conclusion, despite similar fixed airflow obstruction, subjects with a history of asthma have distinct characteristics compared with subjects with a history of COPD and should be properly identified and treated.     

Bronchial hyperreactivity in children with Marfan syndrome

Marfan syndrome is known to have pulmonary manifestations such as pneumothorax. There have been few previous studies of pulmonary function tests and none of bronchial hyperreactivity. Therefore, pulmonary function tests were performed in 11 children with Marfan syndrome and 11 normal children. Bronchial responsiveness was tested in ten of the Marfan patients by methacholine challenge test and response to bronchodilator. Because of disproportionate length of legs in Marfan patients, an "ideal" standing height was calculated from sitting height. Pulmonary function tests, as absolute values or as percent predicted based on "ideal" height, were not different in Marfan patients and normals, although a few individual patients had abnormal function (mostly airway obstruction and hyperinflation). Response to methacholine challenge was positive on forced expiratory volume in 1 second (FEV1), forced expiratory flow between 25 and 75% VC (FEF25-75%), and FEF50%, in 37.5%, 60%, and 70% of tests respectively. A significant response to bronchodilators was obtained in 40% of patients as measured by FEV1, in 90% by FEF25-75% and in 100% by FEF50%. Pulmonary function tests after bronchodilator were significantly higher when compared with values before the bronchodilator as well as with the baseline before methacholine. Therefore, most if not all patients with Marfan syndrome had hyperreactive airways in this relatively small group of patients. Even though only one patient had a diagnosis of asthma, six more had subtle symptoms. It is concluded that tests for bronchial hyperreactivity could be part of the routine investigation in Marfan syndrome. Further studies on larger numbers of patients are still needed.     

Levofloxacin-induced eosinophilic pneumonia complicated by bronchial asthma]

A 76-year-old woman who had complained of cough and productive sputum since mid-January, 1999, was admitted to our hospital with fever and dyspnea on February 4, 1999. She had been treated with levofloxacin at an outpatient clinic. On admission, she had orthopnea, and auscultation revealed coarse crackles and wheeze in the bilateral lung fields. Chest x-ray and CT films showed non-segmental infiltration in bilateral lung fields. Laboratory data revealed eosinophilia in peripheral blood (= 24%) and sputum (= 10%), airflow limitation, hypoxemia (PaO2: 46 Torr), and increased airway responsiveness to methacholine (Dmin: 0.127 units). A bronchoalveolar lavage (BAL) fluid showed increased total cells and a 55% increase in eosinophils, and CD4/CD8 ratio was decreased to 0.8. In addition, IL-5 was increased in BAL fluid. Transbronchial lung biopsy specimens revealed infiltrations of eosinophils in the alveolar and interstitial compartments. Histological features of the bronchial biopsy specimens included increased eosinophils in the submucosa and goblet cell metaplasia. The woman was diagnosed with eosinophilic pneumonia complicated by bronchial asthma. She was given theophylline, pranlukast hydrate, and an inhaled beta 2 receptor agonist (procaterol hydrochloride), and pre-admission drugs including Levofloxacin were discontinued. Her symptoms were improved, peak expiratory flow rate and PaO2 increased, airway responsiveness to methacholine decreased (Dmin: 0.615 units), and radiographic abnormalities disappeared without steroid therapy. A leukocyte migration test for levofloxacin was weakly positive. An environmental provocation test in the patient's home gave negative results. A challenge test for levofloxacin was not performed due to a lack of informed consent. Based on these findings, we diagnosed this case as levofloxacin-induced lung injury manifesting as eosinophilic pneumonia complicated by bronchial asthma. Levofloxacin should be added to the list of agents that can produce eosinophilic pneumonia.     

Atrial septal defect in adults is associated with airway hyperresponsiveness

Objective: The association between secundum atrial septal defects (ASD) and asthma‐ like dyspnea with consequent long‐term pulmonary inhalant use, is poorly understood in adult ASD patients. Airway hyperresponsiveness is suggested to be the underlying mechanism of cardiac asthma from mitral valve disease and ischemic cardiomyopathy. We hypothesized that airway hyperresponsiveness may also be found in adult ASD patients. Our aim was to study airway responsiveness in adult ASD patients before percutaneous closure and at short‐and long‐term postprocedural follow‐up.
Methods: This prospective study included 31 ASD patients (65% female, mean age 49 ± 15y) who underwent spirometry and bronchoprovocation testing pre‐and six‐ month postprocedurally, with additional bronchoprovocation at 2‐year follow‐up. Airway hyperresponsiveness was defined as ≥20% fall of forced expiratory volume in 1‐second (FEV1) following <8.0 mg/mL of inhaled methacholine.
Results: Airway hyperresponsiveness was found in 19/30 patients (63%[95%CI 45%‐81%]; post hoc statistical power = 89%). Asthma‐like symptoms wheezing, chest tightness, and cough were more frequently reported in airway hyperresponsive pa‐ tients. Airway responsiveness was not influenced by successful percutaneous ASD closure, corresponding to persistence of asthma‐like symptoms postclosure. Regardless of airway responsiveness, postprocedural right‐sided reverse remodeling significantly improved dyspnea and pulmonary function.
Conclusions: This study is the firsttoreport ahighprevalenceof airwayhyperresponsiveness in a cohort of unrepaired adult ASD patients, and confirms the association between asthma‐ like symptoms and ASD in adults. Attention to symptoms and pulmonary function should be given during clinical follow‐up of adult ASD patients, both before and long afterrepair.