Chronic cough in children: bronchoalveolar lavage findings.

Isolated chronic cough in childhood is a common complaint. Although the symptom cough is included in the definition of clildhood asthma, there is debate as to whether the majoritv of these children have asthma. The authors studied children with isolated chronic cough looking for evidence of airway inflammation typical of asthma, with increased numbers of airway eosinophils as assessed from bronchoalveolar lavage (BAL). The investigations were carried out on 23 children (median age: 6.7 yrs; range: 1.7-12.75 yrs), attending the Royal Belfast Hospital for Sick Children for elective surgery, who also had a chronic unexplained cough. Written informed consent was obtained from the parent(s) and a nonbronchoscopic BAL was performed. BAL samples were analysed for total and differential white cell counts and also for the inflammatory mediators, eosinophil cationic protein (ECP) and histamine. Results were compared with a group of normal nonatopic children and also a group of atopic asthmatic children, who had been recruited for other studies on airway inflammation. There was a small but statistically significant increase in BAL percentage eosinophils in the children with chronic cough compared with nonasthmatic controls (0.28% versus 0.10%, p=0.03). However, the children with cough had lower percentage eosinophils than the atopic asthmatic controls (0.28% versus 0.66%, p=0.01). Three out of 23 children with chronic cough had BAL eosinophils greater than the normal upper 95% reference interval in BAL. There was a small but statistically significant increase in percentage neutrophils in the children with cough compared with the nonasthmatic controls (5.85% versus 3.21%, p=0.03). Four out of the 23 children had BAL neutrophils greater than the normal upper 95% reference interval in BAL. The authors conclude that only a minority of children with chronic unexplained cough have asthmatic-type airway inflammation. It is speculated that the increased percentage neutrophils in bronchoalveolar lavage from children with cough could relate to underlying persistent airways infection.     

Noneosinophilic CD4 lymphocytic airway inflammation in menopausal women with chronic dry cough

BACKGROUND: Chronic dry cough without dyspnea and wheezing is a well-known condition that is considered to be clinically overrepresented in women. The etiology and morphology remain unknown in many cases despite thorough investigations. DESIGN: To examine inflammatory cells and the lymphocyte profile in the lower airways and blood in women with chronic cough of unknown etiology. SETTING: University hospital department of respiratory medicine. PARTICIPANTS: Twenty-five otherwise healthy women with idiopathic cough and 11 age-matched healthy control women, all nonatopic nonsmokers. MEASUREMENTS: In order to characterize the cough, a careful standardized interview of the patients was made. Lung functions were tested. Cells were collected by BAL and analyzed for differential cell counts separate in the bronchial (first) wash and in the pooled peripheral washes (BAL fluid). The lymphocyte profile in BAL fluid and blood was characterized by dual-color flow cytometry. RESULTS: Eleven female patients formed a specific group with a history of a dry, nonproductive cough that always started in connection with an airway infection coinciding with menopause. Neither exercise, climate, nor seasonal change influenced the cough. BAL fluid contained an increased number of T (CD3+) lymphocytes: median. Seventy-three percent of T lymphocytes were T-helper lymphocytes (CD4+). A median of 57% of the BAL fluid T cells expressed HLA-DR activation marker compared with a median of 20% in the control subjects and in the other 14 included patients with chronic cough but with minor expectoration periodically (p < 0.001 and p < 0.0001, respectively). No differences between the groups were found in the blood. CONCLUSIONS: HLA-DR-activated CD4+ lymphocytic airway inflammation with a low number of eosinophils was identified in a group of nonsmoking, nonatopic otherwise healthy women patients with dry cough of life-long character. The disease appeared exclusively in connection to menopause.     

Comparison of induced sputum with bronchial wash, bronchoalveolar lavage and bronchial biopsies in COPD.

It is unclear how cellular and soluble inflammatory markers in induced sputum relate to markers in lavage fluid and biopsies in chronic obstructive pulmonary disease (COPD). This was investigated and also the possible differences between subjects with COPD and healthy controls assessed. Eighteen nonatopic subjects with COPD and 11 healthy controls were studied. Sputum was induced by inhalation of hypertonic saline. The airways were lavaged, using the first 50 mL for bronchial wash (BW) and the subsequent 150 mL for bronchoalveolar lavage (BAL), and biopsies were taken from subsegmental carinae. Neutrophils were the predominant cell type in sputum in COPD (median 77.3%) but not in BW (5.5%) and BAL fluid (1.7%). Differential cell counts in sputum did not correlate with the counts in BW or BAL fluid or biopsies, whereas sputum eosinophil cationic protein (ECP) levels correlated with BW fluid ECP levels (p=0.66, p=0.007) and sputum interleukin-8 (IL-8) concentration with BAL fluid IL-8 concentration (p= 0.52, p=0.026). Subjects with COPD had a higher percentage of sputum neutrophils and eosinophils and higher concentrations of ECP and IL-8 than healthy controls. The higher percentages of eosinophils and concentrations of ECP were also seen in BW and BAL fluid. Finally, higher numbers of macrophages and eosinophils were found in biopsies. In conclusion, induced sputum is derived from a different compartment from BW and BAL fluid and biopsies. Induced sputum may be useful for studying the contribution of luminal neutrophils and eosinophils in chronic obstructive pulmonary disease.     

A pathogenic triad in chronic cough: asthma, postnasal drip syndrome, and gastroesophageal reflux disease.

BACKGROUND: Coughing may be produced by a number of different disorders in distinct anatomic sites. Chronic cough causes major functional limitation in a considerable patient population and requires careful evaluation. METHODS: Seventy-eight nonsmoking patients of both genders who complained of cough for > or =3 weeks and had normal findings on plain chest radiographs were studied prospectively. Their histories were obtained, and physical examinations were performed. The diagnostic workup included pulmonary function tests, CT of the paranasal sinuses and chest, carbachol provocation test, fiberoptic rhinoscopy, fiberoptic bronchoscopy, and 24-h esophageal pH monitoring. The final diagnosis depended on clinical, radiologic, and laboratory findings; a successful response to therapy was required for confirmation. RESULTS: The causes of chronic cough were determined in all patients. Coughing was due to a single cause in 30 patients (38.5%) and multiple causes in 48 patients (61.5%). The five most important causative factors were asthma (46 patients; 58.9%), postnasal drip syndrome (PNDS; 45 patients; 57.6%), gastroesophageal reflux disease (GERD; 32 patients; 41.1%), bronchiectasis (14 patients; 17.9%), and tracheobronchial collapse (11 patients; 14.1%). INTERPRETATION: Asthma, PNDS, and GERD, alone or in combination, were responsible for 93.6% of the cases of chronic cough. The presence of these three conditions was so frequent that the expression "pathogenic triad of chronic cough" should be acknowledged in specialized literature. It is essential to consider pulmonary and extrapulmonary causes in order to prescribe a successful specific therapy for chronic cough.     

嗜酸粒细胞性支气管炎的气道炎症和临床特点

目的　探讨嗜酸粒细胞性支气管炎 (eosinophilicbronchitis,EB)的诊断、治疗及其气道炎症特点。方法　采用Irwin慢性咳嗽解剖学诊断程序 ,对 86例慢性咳嗽患者进行病因诊断 ;通过诱导痰 ,分析痰液中细胞分类 ,分别采用荧光酶免疫法、酶联免疫吸附法测定诱导痰上清液中嗜酸粒细胞阳离子蛋白 (ECP)、白细胞介素 8(IL 8)的浓度 ,并以 9例正常人和 9例典型哮喘患者作对照组 ;吸入布地奈德干粉剂 2 0 0～ 4 0 0 μg ,每天 2次 ,治疗 4周 ,部分患者同时口服泼尼松 10～ 15mg/d或甲泼尼龙 8～ 12mg/d ,1周。结果　本组有 13例符合EB诊断 ,占慢性咳嗽的 15 % ,多表现为慢性干咳 ,肺功能正常 ,组胺激发试验阴性。EB诱导痰嗜酸粒细胞 (Eos)为 0 186 2± 0 16 32 ,ECP浓度为(2 5 3± 2 0 7)mg/L ,均较正常人升高 (P <0 0 1) ;糖皮质激素治疗 1周后 ,13例患者的咳嗽均消失。结论　EB是引起慢性咳嗽的一个重要原因 ,气道具有以Eos为主的炎症 ,糖皮质激素治疗效果良好。     

Chronic cough and gastro-oesophageal reflux: a double-blind placebo-controlled study with omeprazole.

Gastro-oesophageal reflux (GOR) is an important cause of chronic cough. There has been a lack of placebo-controlled trials treating GOR related chronic cough with antireflux therapy. The aim of this study was to determine the efficacy of omeprazole on GOR related chronic cough. After excluding other common causes of cough, oesophageal pH monitoring was performed on 48 patients with chronic cough. Twenty-nine patients found to have GOR were randomized in a double-blind fashion to receive omeprazole 40 mg o.d. or placebo for 8 weeks. After a 2-week washout period, patients were crossed over to the other treatment. Symptoms were recorded daily in a diary. Twenty-one patients completed both treatment periods. Cough (p=0.02) and gastric symptoms (p=0.003) improved significantly during the omeprazole treatment in twelve patients who received placebo during the first and omeprazole during the second 8-week period. In nine patients who received omeprazole during the first 8-week period, amelioration in cough reached statistical significance only after cessation of omeprazole. Gastric symptoms also remained minor during placebo in these nine patients. Omeprazole 40 mg o.d. seems to improve chronic cough in patients with gastrooesophageal reflux and the effect of omeprazole in ameliorating both cough and reflux symptoms continues after treatment ceases.     

Inflammatory cells and eosinophilic activity in asthmatics investigated by bronchoalveolar lavage. The effects of antiasthmatic treatment with budesonide or terbutaline

We investigated the constituents of bronchoalveolar lavage (BAL) regarding cell profiles and released eosinophilic cationic protein (ECP) in 11 patients treated occasionally with inhaled bronchodilators (Group A) and 11 patients treated regularly with inhaled corticosteroids (Group B). A normal, healthy control group of 12 subjects was also recruited. Compared with Group A, Group B had a reduced recovery percentage of infused volume (p less than 0.05) and total cell number (p less than 0.01). Compared with the control group, there was a significant increase in the percentage of eosinophils (p less than 0.05) in both groups of asthmatics. In Group A there was also a significant increase in mast cells (p less than 0.05), serum-ECP (p less than 0.05), and BAL-ECP (p less than 0.001). No correlations between any of the cell variables and the level of airway responsiveness measured as PC20 histamine were found in any group. Group A patients were investigated twice--before and after 4 wk of randomly allocated treatment with either a regular beta-2-receptor agonist (terbutaline 250 micrograms, two puffs four times a day) or a regularly inhaled corticosteroid (budesonide 200 micrograms twice a day). The BAL differential cell counts were similar and not significantly affected by either treatment. However, BAL-ECP levels were decreased by budesonide treatment (p less than 0.05). ECP levels in serum and BAL were significantly correlated (p less than 0.05 to 0.001). The eosinophilic cell involvement in asthma is further emphasized by this study but the increase in numbers of eosinophils seems less important than their activity, here measured as release of one degranulation product, ECP. To suppress disease activity, repeated long-term treatment is important, but clear preference for either treatment cannot be given on the basis of our present results.     

Detection of Eosinophils in Hypertonic Saline-Induced Sputum in Patients with Chronic Nonproductive Cough

This study was conducted to examine (1) whether an appropriate sputum can be obtained by inducing with inhalation of hypertonic saline in patients with chronic nonproductive cough and (2) whether eosinophils can be detected in the induced sputum. Appropriate samples were obtained by the induction in 25 of 31 patients with bronchial asthma (BA), 12 of 17 patients with cough-variant asthma (CVA), 17 of 20 patients with bronchodilator-resistant cough associated with atopy (atopic cough, AC), and 23 of 25 healthy subjects. Eosinophils were detected in the successfully induced sputum in 100%, 66.6%, and 88.2% of the patients with BA, CVA, and AC, respectively. Detection of eosinophils in induced sputum may be the initial diagnostic procedure for nonproductive cough of allergic nature.     

Elevated bronchoalveolar lavage fluid histamine levels in allergic asthmatics are associated with increased airway obstruction

Bronchoalveolar lavage (BAL) fluid was evaluated for histamine and tryptase levels in 61 samples (46 samples from 24 atopic asthmatics, seven samples from seven patients with allergic rhinitis, and eight samples from eight normal volunteers). Asthmatics and patients with allergic rhinitis had significantly higher BAL histamine than did normal subjects (169 +/- 22, 141 +/- 23, 42 +/- 6 pg/ml, respectively; p less than 0.05, both comparisons). BAL fluid tryptase levels were also higher in asthmatics and patients with allergic rhinitis than in normal subjects (0.36 +/- 0.03, 0.38 +/- 0.05, 0.23 +/- 0.04 ng/ml, respectively; p less than 0.05, both comparisons); however, levels of tryptase and histamine in BAL were not correlated (r = -0.03 in the group as a whole, r = -0.12 in the asthmatic group). BAL concentration of histamine correlated inversely with FEV1 percent predicted in the asthmatic group (r = -0.44, p less than 0.005). Asthmatics with high BAL fluid histamine (greater than or equal to 100 pg/ml, n = 23) had lower FEV1 percent predicted (80 +/- 3% versus 96 +/- 3%, p = 0.0005), lower FEV1/FVC ratio (72 +/- 1% versus 77 +/- 2%, p less than 0.05), higher percentage of BAL eosinophils (2.2 +/- 0.4% versus 0.6 +/- 0.1%, p less than 0.002), and greater airway responsiveness (lower PD20 [13.1 +/- 3.4 versus 41.5 +/- 13.7 cumulative breath units, p less than 0.05]) compared with asthmatics with low BAL fluid histamine (less than 100 pg/ml, n = 23).(ABSTRACT TRUNCATED AT 250 WORDS)     

Is there an association between angiotensin-converting enzyme gene variants and chronic nonproductive cough?

BACKGROUND: It is unclear why some patients develop a chronic nonproductive cough. Angiotensin-converting enzyme (ACE) inactivates tussive peptides in the airways such as bradykinin and tachykinins. An insertion/deletion polymorphism in the ACE gene accounts for variation in ACE levels, and patients with the II genotype have lowest serum ACE levels compared with ID and DD genotypes. We hypothesized that the II genotype would be associated with increased risk of developing a chronic cough. MATERIALS AND METHODS: We recruited 47 patients (33 women), referred for evaluation of cough (median cough duration, 24 months; range, 2 to 240 months). Cough patients were evaluated using a comprehensive diagnostic protocol, and cough reflex sensitivity was measured using a capsaicin inhalation challenge. ACE genotyping was performed on DNA samples from patients using the polymerase chain reaction followed by agarose gel electrophoresis. ACE genotypes in patients with chronic cough were compared with those in 199 healthy control subjects. Serum ACE levels were determined using a colorimetric assay. RESULTS: Genotype frequencies for the ACE gene were similar between patients and control subjects. There was no correlation between capsaicin sensitivity and ACE genotypes or serum ACE levels. CONCLUSION: Susceptibility to develop chronic cough is not associated with ACE genotype.     

Calcitonin gene-related peptide relates to cough sensitivity in children with chronic cough.

Airway neuropeptides, in particular calcitonin gene-related peptide (CGRP), are likely to be important in the pathogenesis of chronic cough. The present authors evaluated the following: 1) the relationship between cough sensitivity and bronchoalveolar lavage (BAL) neuropeptides; and 2) the effect of reflux oesophagitis (RO) on cough, cough sensitivity and BAL neuropeptides in children not selected for cough. It was hypothesised that CGRP would be increased in children with chronic cough and would relate to cough sensitivity. Capsaicin cough sensitivity was performed in children undergoing gastro-duodenal endoscopy. CGRP, substance P and neurokinin A were measured in BAL obtained nonbronchoscopically. Children were defined as "coughers" if chronic cough was present. Coughers (n = 21) had significantly reduced cough sensitivity but were just as likely as noncoughers (n = 19) to have RO. The median CGRP was significantly higher in coughers with oesophagitis than in noncoughers with oesophagitis. CGRP significantly negatively correlated to cough sensitivity in coughers but not in noncoughers. Elevated calcitonin gene-related peptide, but not substance P or neurokinin A, is only associated with chronic cough in children when oesophagitis coexists. Calcitonin gene-related peptide in bronchoalveolar lavage relates to cough sensitivity and is likely to be important in the pathophysiology of chronic cough.     

The effect of processing on inflammatory markers in induced sputum.

The effects of the mucolytic agent, dithioerythritol (DTE), and the temperature at which sputum processing is conducted on cellular and biochemical markers in induced sputum was assessed. Samples from healthy and atopic asthmatic subjects were treated with either DTE or phosphate-buffered saline (PBS) at 22 or 37 degrees C and compared for cell counts and concentrations of histamine, tryptase, eosinophil cationic protein (ECP), free interleukin (IL)-8, immunoglobulin (Ig)A, IL-8/IgA complexes and secretory component (SC). In addition, the influence of DTE on in vitro mediator release from blood eosinophils, basophils and bronchoalveolar lavage (BAL) mast cells was studied. Processing with DTE improved cytospin quality and increased the cell yield and measurable ECP, tryptase, IgA and SC, but reduced levels of histamine in PBS-treated samples and had no effect on IL-8. Cell counts or mediator levels were similar when sputum was processed at 22 or 37 degrees C, even though DTE induced blood basophils and BAL mast cells to release histamine at 37 degrees C. In spiking experiments, recovery of added ECP, tryptase, total IL-8 and histamine from sputum was similar in DTE- and PBS-processed sputum, but reduced for free IL-8 in PBS-treated samples. In conclusion, dithioerythritol improves cell and mediator recovery without causing cell activation when sputum processing is conducted at room temperature. The extent of recovery depends on the mediator studied.     

Airflow obstruction in nonsmoking,asbestos-and mixed dust-exposed workers

Obstructive changes in small airways have been described in patients exposed to asbestos and other mineral dusts. The physiologic significance of these small airways abnormalities and their relationship to dust burden and alveolitis remain unclear. We performed bronchoalveolar lavage (BAL) in 30 nonsmoking and 30 age-matched smoking subjects, all with mild asbestos and mixed dust exposure, to determine if parameters of lung dust burden correlated with spirometric evidence of airflow obstruction. Seventeen of 30 nonsmoking subjects and 24 of 30 smoking subjects met spirometric criteria for airflow obstruction. There were significantly more obstructed subjects in both dust exposed groups (P < 0.05) than in an age-matched nondust exposed group. There was, however, no significant difference in the number of obstructed subjects between the smoking and nonsmoking groups. There was no correlation in either group between airflow obstruction and total or differential cell counts, ferruginous bodies, total asbestos fibers, or the percent of free silica in the particulate fraction recovered by BAL. We conclude that evidence of small airways obstruction occurs commonly in occupationally dust exposed subjects and appears to be related to dust exposure per se and not to alveolar inflammation or fiber retention, important factors in the development of alveolitis and interstitial lung disease. Offprint requests to: D. E. Griffith.     

Interpreting the histopathology of chronic cough: a prospective, controlled, comparative study

HYPOTHESIS: Trauma from chronic coughing produces airway inflammation similar to diseases causing cough. DESIGN: Prospective, cross-sectional, controlled, clinicopathologic correlation study in four groups: group 1, cough from intrapulmonary diseases; group 2, cough from extrapulmonary diseases; group 3, cough that was unexplained; and group 4, nonsmoking, asymptomatic control subjects. METHODS: Patients with chronic cough underwent a standardized workup including endobronchial biopsies before treatment. Causes were determined by a favorable response to therapy. Bronchial biopsy samples from control subjects were obtained from surgical specimens. RESULTS: There were 24 adult subjects (13 women and 11 men) with mean cough duration of 8.6 +/- 7.4 years (+/- SD). Thirteen patients had cough due to a specific disease: intrapulmonary diseases in 5 patients, and extrapulmonary diseases in 8 patients. Eleven patients had unexplained cough. Compared to control subjects, there was minimal-to-moderate chronic inflammation in all coughers (p < or = 0.0004), in group 1 (p < or = 0.039), group 2 (p = 0.061), and group 3 (p < or = 0.025) diseases that were not correlated with cough duration. There was no difference in type of inflammation, cough duration, or smoking history between groups, nor were there histologic differences between subjects with explained causes of cough compared with unexplained cough. CONCLUSIONS: Our findings suggest that airway inflammation associated with chronic cough, assessed on morphologic appearance and inflammatory cell counting in hematoxylin-eosin-prepared samples, may be due to the trauma of coughing, and the inflammation may be similar to that seen with diseases putatively thought to cause chronic cough. Investigators must be cautious when attributing pathogenic importance to observed inflammatory changes in airways of coughing subjects.     

Post-nasal drip syndrome—a symptom to be sniffed at?

The syndrome or pseudo-syndrome of post-nasal drip (PNDS) represents a diagnostic label which is unhelpful in the understanding of chronic cough. There is no accepted definition of PNDS and no accepted method of measurement. The symptom of mucus dripping down the back of the throat occurs in normal subjects and is also reported by many patients in ENT clinics who do not have a cough. The lack of any clear pathological or biochemical tests makes the syndrome both a catch-all and a dustbin.     

Post-nasal drip syndrome--a symptom to be sniffed at?

The syndrome or pseudo-syndrome of post-nasal drip (PNDS) represents a diagnostic label which is unhelpful in the understanding of chronic cough. There is no accepted definition of PNDS and no accepted method of measurement. The symptom of mucus dripping down the back of the throat occurs in normal subjects and is also reported by many patients in ENT clinics who do not have a cough. The lack of any clear pathological or biochemical tests makes the syndrome both a catch-all and a dustbin.     

Use of segmental airway lavage to obtain relevant mediators from the lungs of asthmatic and control subjects

Studies have demonstrated that increased amounts of histamine in the airways of asthmatic patients are associated with increased airway reactivity. However, using routine bronchoalveolar lavage (BAL), histamine can be detected in only a portion of asthmatic subjects and a minority of control populations. To obtain relevant mediators from the airways in higher concentrations by avoiding the dilution inherent with a standard BAL, a technique was developed to lavage isolated airway segments of the human lung that employed a double-lumen bronchoscope and a balloon-tipped catheter. Lavage fluid obtained by this method yielded significantly higher concentrations of histamine than that obtained with routine BAL (asthmatic subjects, 2,403 +/- 633 pg/ml vs 188 +/- 42 pg/ml; rhinitis subjects, 533 +/- 187 pg/ml vs 113 +/- 53 pg/ml; normal subjects, 174 +/- 63 pg/ml vs 11 +/- 11 pg/ml). Similar findings were also noted for prostaglandin D2 (PGD2). Segmental airway lavage also resulted in higher lavage fluid concentrations of LTB, than routine BAL. Segmental airway lavage should help in studying the relationship of mast cell degranulation to airways reactivity in both asthmatic and other study populations.     

Persistent high BAL fluid granulocyte activation marker levels as early indicators of bronchiolitis obliterans after lung transplant.

The major cause of mortality in the long-term in lung transplant recipients is chronic rejection. This is a fibroproliferative process in the small airways leading to obliterative bronchiolitis and progressive loss of lung function, both constituting the clinical entity bronchiolitis obliterans syndrome (BOS). Granulocyte activation has been implicated as one factor behind BOS. Granulocyte markers in bronchoalveolar lavage (BAL) fluid were prospectively and longitudinally studied in order to identify possible association with BOS. BAL fluid from 266 bronchoscopy procedures performed in twelve single lung, eight bilateral lung and five heart/lung transplant recipients were analysed. The majority (19 of 25) were studied for a period of 2 yrs after surgery. Myeloperoxidase (MPO), eosinophil cationic protein (ECP) and interleukin-8 (IL-8) levels were used as indirect markers of activation and attraction of granulocytes. Five patients developed BOS. Ninety-eight episodes of acute rejection, nine of bacterial infection, 19 of cytomegalovirus pneumonitis, nine of Pneumocystis carinii infection, two of aspergillus infection and two of respiratory syncytial virus infection were diagnosed. BOS patients had significantly higher mean levels of MPO, ECP and IL-8 compared to patients without BOS, irrespective of acute rejection status. Over time, the five patients with BOS had significantly elevated BAL fluid levels of MPO and ECP as well as neutrophil percentages, and in four patients this increase preceded the clinical diagnosis of BOS by several months. Elevated bronchoalveolar lavage fluid neutrophil percentage as well as levels of the granulocyte activation markers myeloperoxidase and eosinophil cationic protein appear to be early signs of development of BOS in lung transplant recipients.     

Bronchial biopsy and sequential bronchoalveolar lavage in atopic cough: In view of the effect of histamine H1-receptor antagonists

We have shown that some patients presenting with chronic bronchodilator-resistant non-productive cough have global atopic tendency, airway cough hyper-sensitivity without non-specific bronchial hyperresponsiveness and eosinophilic inflammation of the trachea and bronchi, abbreviated as atopic cough (AC). Histamine H₁ receptor antagonists are effective in relieving the cough in some patients with AC but not in others in whom corticosteroids are needed to improve the cough. The aim of the present study was to compare the intensity of eosinophil infiltration in biopsied bronchial submucosa and sequential bronchoalveolar lavage (SBAL) fluids between two subgroups of patients with AC: (i) group A, successfully treated with histamine H₁ receptor antagonists; and (ii) group B, requiring corticosteroids. Sequential BAL was performed using three 50 mL aliquots of physiologic saline solution and then bronchoscopic bronchial biopsy was performed in group A (n = 9) and B (n = 9) patients. Sequential BAL was also performed in normal controls (NC; n = 13). The first SBAL fraction was analyzed as bronchial lavage fluid (BLF) and the mixed fluid of the second and third SBAL fractions as bronchoalveolar lavage fluid (BALF). The number of eosinophils in the bronchial subepithelium was significantly (P = 0.0134) greater in group B patients (median 8.3 cells/mm²; range 3.6–21.9 cells/mm²) compared with group A (median 3.6 cells/mm²; range 0–10.0 cells/mm²). However, There were no significant differences in the number or percentage of eosinophils in BLF or BALF between group A, group B and NC subjects. These findings confirm that eosinophils do not infiltrate the peripheral airways of AC and suggest that corticosteroids are required to relieve the cough in more severe illness of AC, in which submucosal eosinophilic inflammation of the central bronchi is more intensive compared with the milder illness successfully treated with histamine H receptor antagonists.     

Airway inflammation as an assessment of chronic nonproductive cough

OBJECTIVES: The possibility that a bronchial inflammatory process could be involved with a chronic nonproductive cough without other potential causes such as postnasal drip syndrome, bronchial asthma, gastroesophageal reflux, chronic bronchitis, bronchiectasis, or the use of angiotensin-converting enzyme inhibitors has not been clearly described. We investigated the possibility that a chronic nonproductive cough without other potential causes is associated with airway inflammation, and if this is so, what the relationship might be between this inflammation and the possible etiology of the cough. SUBJECTS: Twenty-five adults with chronic nonproductive cough as an isolated symptom over a 3-week period, and 5 healthy control subjects were studied. MEASUREMENTS AND RESULTS: Clinical assessments, cough scores, methacholine challenges, allergy skin prick tests, and bronchoscopies for bronchial biopsies were performed. In the bronchial biopsies, the patients were divided into the following two subgroups: 21 patients who were infiltrated with eosinophils vs the healthy control group (median, 12.0 vs. 0.0 cells/mm(2), respectively; p < 0.01); and 4 patients who were infiltrated with lymphocytes vs the healthy control group (median, 84.5 vs. 22.0 cells/mm(2), respectively; p < 0.01). With the methacholine challenge test, 5 of the 21 eosinophil-infiltrated patients received diagnoses of cough-variant asthma, and the other 16 patients received diagnoses of eosinophilic bronchitis. In the lymphocyte-infiltrated group, all four patients received diagnoses of lymphocytic bronchitis. CONCLUSIONS: These results suggest that a chronic nonproductive cough as an isolated symptom is associated with airway inflammation due to eosinophil and lymphocyte infiltration. The causes of the chronic nonproductive cough were eosinophilic bronchitis, cough-variant asthma, and lymphocytic bronchitis.