Comparison of atopic and nonatopic children with chronic cough: bronchoalveolar lavage cell profile

Chronic cough is a common complaint in children and its relationship with asthma is controversial. The aim of the present study was to determine the pattern of airway inflammation in atopic and nonatopic children with chronic cough, and to investigate whether atopy is a predictive factor for eosinophilic inflammation in cough. Bronchoalveolar lavage (BAL; three aliquots of 1 ml/kg saline) was performed in the right middle lobe of 24 (11 atopic and 13 nonatopic) children with persistent cough (8 females, 16 males), mean age 4.7 years (range: 1-11). Atopy was defined as an elevated total serum IgE or a positive RAST test. Both atopic and nonatopic children with persistent cough had an increase in total cells/ml in BAL (atopic: median 39 x 10(4), range: 20-123; nonatopic: median 22 x 10(4), range: 17-132) compared to nonatopic controls (median 11 x 10(4), range 9-30). The increases were mainly in neutrophils (atopic: median 17%, range 2.5-88.5%; nonatopic: median 6%, range 1.0-55.0%) compared to controls (median 1.55%, range 0.5-7.0%; atopics vs. controls, P < 0.005). There were no significant increases in eosinophils, lymphocytes, epithelial cells, or mast cells. Eosinophils were elevated in only 5/11 atopic and none of the nonatopic children. The increased percentage of neutrophils in the BAL fluid of atopic and nonatopic children with persistent cough could be due to an underlying inflammatory process driving the cough, or even conceivably, due to the effect of coughing itself. In this highly selected series, the absence of eosinophilic inflammation in the majority suggests that most would be predicted not to respond to inhaled corticosteroid therapy. This study underscores the need to be cautious about treating coughing children with inhaled corticosteroids, even in the context of a tertiary referral practice.     

Bronchoalveolar lavage findings in patients with chronic nonproductive cough.

Mast cells and eosinophils may play a role in the pathophysiology of chronic cough in nonasthmatics. It is unknown, however, whether degranulation of these cells occurs in the airways of such patients. Thirty-five nonsmoking patients referred with a chronic nonproductive cough (mean cough duration 76.2 months) were evaluated using a comprehensive diagnostic protocol. Bronchoalveolar lavage (BAL) cell differentials and BAL histamine, tryptase and eosinophilic cationic protein (ECP) concentrations were determined. Ten nonsmoking healthy volunteers served as controls. Diagnostic subgroups were identified: eight postnasal drip syndrome (PNDS), seven cough variant asthma (CVA), seven gastro-esophageal reflux (GOR), seven dual aetiology and six idiopathic. Nonasthmatic coughers (NAC) were characterized as those patients without bronchial hyperresponsiveness on histamine challenge and whose cough had either responded to therapy for PNDS or GOR or failed to improve with antiasthma therapy. There was a significant increase in both eosinophil and mast cell numbers (p<0.05) and in histamine levels (p = 0.027) when NAC patients were compared with controls. Tryptase and ECP levels were elevated in 7 of 23 and 6 of 23 NAC patients, respectively. In conclusion, airway inflammatory cell numbers are not only increased but also activated, suggesting an important role for airways inflammation in the pathophysiology of chronic nonproductive cough.     

Investigation of children with chronic nonspecific cough: any clinical benefit of bronchoscopy and bronchoalveolar lavage?

Chronic cough can be a complicated and frustrating diagnostic dilemma. The aim of this study was to identify the possible causes of chronic nonspecific cough in seemingly healthy children using fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL). Eighteen children responded to criteria of selection for chronic cough. The average age was 5.8 years (range, 1.7-10.7 years) and BAL findings were compared with those of 16 nonatopic controls. Children with chronic cough had an increased percentage of BAL neutrophils in comparison with the control group (p = 0.098). Using a BAL neutrophil percent cutoff of 17%, 6 children had high BAL neutrophils (HBNs; median, 77%; range, 27-96%) and 12 children had normal BAL neutrophils (NBNs; median, 3%; range, 0-13%). In the HBN group, FOB showed endoscopic abnormalities in four patients, BAL culture was positive in three patients, and chest x-ray (CXRs) showed minimal densities in four. The IL-8 levels showed a significant increase with respect to the NBN group (p = 0.005). The combination of endoscopic anomalies, BAL culture, BAL IL-8 levels, and minor CXR changes can support the diagnosis of subclincal infection in seemingly healthy children with chronic nonspecific cough and HBN.     

Diagnostic bronchoalveolar lavage in children with AIDS

Between October, 1985 and May 1987, 29 children (mean age 22 +/- 22 months, range 2-54 months) with AIDS or ARC developed acute respiratory illness. The initial diagnostic procedure was flexible fiberoptic bronchoscopy, with bronchoalveolar lavage (BAL). BAL was positive for Pneumocystis carinii in 14 and for respiratory syncytial virus, Staphylococcus aureus, and Escherichia coli in 3 additional patients. Subsequent lung tissue analysis and/or clinical course suggested no false negative lavages. Complications possibly related to the procedure occurred in two patients. We find BAL an effective diagnostic technique in these patients, offering a less invasive alternative to open lung biopsy.     

Acute eosinophilic pneumonia due to toxocariasis with bronchoalveolar lavage findings.

A previously healthy young man presented with breathlessness, diffuse pulmonary infiltrates on the chest x-ray film, and a high degree of peripheral blood eosinophilia. Analysis of bronchoalveolar lavage (BAL) fluid showed 64 percent eosinophils. A diagnosis of toxocariasis was eventually reached on the basis of a positive enzyme-linked immunosorbent assay (ELISA) for Toxocara canis. The routine performance of the ELISA test for Toxocara in the diagnostic approach to pulmonary infiltration with eosinophilia could reveal an undetermined, sometimes unsuspected, number of cases of adult toxocariasis with pulmonary involvement. A high degree of eosinophilia in the differential cell count of BAL fluid may eventually prove to be a useful clue in favor of such a diagnosis.     

Nonbronchoscopic approach to bronchoalveolar lavage in children with artificial airways.

Bronchoalveolar lavage (BAL) performed with a fiberoptic bronchoscope (FOB) is a useful method for sampling alveolar contents. Since the smallest FOB with a channel has a diameter of 3.6 mm, BAL is difficult to accomplish through artificial airways (AA) less than 5.0 mm I.D. We used a 4F balloon wedge pressure catheter to perform BAL through small AA. Supplemental O2 or ventilatory support was delivered via an adaptor through which the catheter was introduced. After it was passed distal to the AA, the balloon was inflated with normal saline (NS) to a predetermined volume, and advanced until resistance was felt. The balloon was deflated, advanced slightly, and then reinflated to achieve airway occlusion. Five aliquots of 0.75 mL/kg of NS were used for BAL. The procedure was performed in 20 children from 1 month (950 g) to 6 1/2 years of age (median, 9 months). All specimens contained abundant alveolar macrophages, indicating good recovery of alveolar contents. Clinically significant information was obtained in 17 (85%) cases, and no patient required an open lung biopsy. In conclusion, nonbronchoscopic bronchoalveolar lavage is a valuable method for obtaining alveolar contents in children with small AA that preclude the use of an FOB, and it obviates the need for open lung biopsy in many patients. This technique could be used as a research tool for measuring constituents of alveolar contents in infants and small animals.     

Lipid-laden macrophage index and inflammation in bronchoalveolar lavage fluids in children.

The presence of lipids in alveolar macrophages has been used clinically as an indicator of aspiration, a process associated with increased lung inflammation in animal models. The hypothesis is that the quantity of lipids in alveolar macrophages, measured as lipid-laden index (LLI), would correlate with lung inflammation in paediatric patients. Children with chronic respiratory symptoms (21 cystic fibrosis (CF), 24 non-CF) underwent flexible bronchoscopy with bronchoalveolar lavage (BAL) and 24-h intraoesophageal pH monitoring for clinical indications. Total cell counts, number and per cent of neutrophils and macrophages, and LLI were determined in the bronchoalveolar lavage fluids (BALF) from all children. BALF were also obtained from eight healthy, young nonsmoking adults for comparison. LLI in non-CF children were 6.9 +/- 3.5 (mean +/- SEM) which were higher than LLI in healthy adults (1.0 +/- 0.4), (p=0.045). Children with CF had very high LLIs (19.2 +/- 4.5) compared with both healthy adults (p=0.014) and children without CF (p=0.045). LLI did not correlate with airway inflammation in any group. LLI in children with abnormal pH probes had a tendency to be higher than in children with normal pH probes, but the difference was not significant (p=0.098). It is concluded that the lipid-laden index was significantly elevated in children with chronic respiratory symptoms compared with healthy adults, and in children with cystic fibrosis compared with those who have other chronic respiratory conditions. However, the lipid-laden index did not correlate with the quantity of bronchoalveolar lavage fluid inflammation. The lipid-laden index in children may, in part, reflect processes other than aspiration, such as airways obstruction.     

Differential cytology of bronchoalveolar lavage fluid in asthmatic children

Although asthma usually begins in childhood, limited information is available as to the inflammatory reaction of asthmatic children compared to adults and the influence of age. We investigated the cytology of bronchoalveolar lavage fluid (BALF) in 39 newly diagnosed wheezy children (minimum of 3 wheezing episodes during last 6 months): 21 allergic and 18 nonallergic subjects. None had received antiinflammatory treatment. Bronchoalveolar lavage (BAL) was performed, instilling 0.5 ml.kg(-1) body weight of warmed saline in 4 successive fractions. The first 2 aliquots (BALF 1) were pooled for microbiology and cytology, and the last 2 (BALF 2) for cytology only. Recovery correlated inversely with age, the most significant being for BALF 2 (r = -0.52, P = 0.001). Children under 2 years of age had larger amounts of ciliated columnar and goblet cells (P = 0.0074). Other cell types did not show age dependency. Differential cytology was characterized by a high number of creola bodies, bronchial epithelial cells (M = 68 x 10(3).ml(-1), R = 5-349), and neutrophils (M = 92 x 10(3).ml(-1), R = 0-1,257). Eosinophils were the only cells distinguishing allergic from nonallergic subjects (P = 0.003). The 16 children with positive microbiology had more neutrophils than the noninfected (P = 0.008), the latter still having more neutrophils than found in adults. These data suggest a limited age dependency in BALF cytology. Differential cytology in BALF might be helpful in differentiating asthma in children. Neutrophil inflammation might be more important than in adults.     

Use of bronchoalveolar lavage in immunocompromised children with pneumonia

Because pneumonia in the immunocompromised host presents a diagnostic dilemma to the pediatrician, we prospectively studied the use of bronchoalveolar lavage (BAL) with flexible fiberoptic bronchoscopy in 14 immunocompromised children with pneumonia over a 5-month period. The children received immunosuppressive agents because of organ transplants, cancer, or systemic lupus erythematosus. A diagnosis was made by BAL in 10 (71%) of the 14 children. Pathogenic organisms included Pneumocystis carinii in six, cytomegalovirus (CMV) in two, Aspergillus fumigatus in one, and a mixed infection of Candida albicans and CMV in one. There were no complications. Because BAL by flexible fiber-optic bronchoscopy is a rapid and safe procedure and a diagnosis can be made in a majority of cases, we recommend its use in immunocompromised children with pneumonia before resorting to lung biopsy.     

Interlobar differences in bronchoalveolar lavage fluid from children with cystic fibrosis.

Bronchoalveolar lavage (BAL) performed in specialist centres has improved the understanding of infant cystic fibrosis (CF) lung disease. As most researchers sample from a single lobe, it was determined whether BAL results could be generalized to other lung segments. Thirty-three CF children, aged 1.5-57 months, underwent in random order sequential BAL of their right middle and lingula lobes. Specimens from each lobe had separate quantitative bacteriology, cytology and cytokine analysis. Bacterial counts > or = 1 x 10(5) colony forming units (cfu) x mL(-1) were observed in nine (27%) subjects, including six involving only the right middle lobe. These six children had similar inflammatory indices in their right middle and lingula lobes, and interleukin (IL)-8 concentrations in the latter were significantly higher than that observed within the lingula lobes of the 24 CF children with bacterial counts < 1 x 10(5) cfu x mL(-1). Lingula neutrophil and IL-8 levels correlated best with right middle lobe bacteria numbers. This observational study in cystic fibrosis children suggests that while inflammation is detected in both lungs, bacterial distribution may be more inhomogeneous. Bronchoalveolar lavage microbiological findings from a single lobe may therefore, not be generalized to other lung segments. When performing bronchoalveolar lavage in cystic fibrosis children, it is important to sample from multiple sites.     

Correlation of bronchoalveolar lavage and clinical and functional findings in asbestosis

Respiratory clinical, radiographic, and functional findings were assessed and correlated with bronchoalveolar lavage (BAL) cellular changes in 52 asbestos workers (27 with and 25 without asbestosis) and in 15 control subjects without asbestos exposure. Subjects with asbestosis had a moderate neutrophilic alveolitis (7.8 +/- 5%) compared with the other groups (p less than 0.001) that was correlated with the presence of crackles (p = 0.03) and PaO2 (p less than 0.05) and AaPO2 at rest (p less than 0.05) values. Asbestos bodies (AB) in BAL were quantitated in 34 of the 52 asbestos workers (21 with and 13 without asbestosis) and in the control group. They were present in 83% of asbestos workers but they were absent in the latter. No significant differences were observed in the number of AB between those asbestos workers with and without lung disease. We conclude that crackles on auscultation and PaO2 and AaPO2 values may well be good indicators of the staging of neutrophilic alveolitis in asbestosis. In contrast, the amount of AB in BAL is not a reliable marker of asbestos lung fibrosis.     

Adjustment of bronchoalveolar lavage volume to body weight in children

To define the amount of epithelial lining fluid (ELF) that is recovered during bronchoalveolar lavage (BAL) in the pediatric age group, we measured albumin and urea concentrations in serum and BAL fluid (BALF) of 37 children aged 3–15 years without bronchopulmonary disease. The children were studied while undergoing elective surgery for non-pulmonary illnesses using a BAL protocol adjusted to body weight. ELF increased with age in proportion to increases in lavage volume. When corrected for the child's weight, approximately 20 μl ELF/kg body weight were recovered throughout the age range. ELF derived by determining albumin or urea concentrations in BALF were significantly correlated; however, considerable variability was observed in older children when the urea method was used. This was likely due to the increase in dwell time that is known to affect urea concentrations in BALF. In children ELF/100 ml BALF was higher than in adults, suggesting a greater permeability of the alveolar membrane in children. These data show that a BAL protocol adjusted to body weight will yield constant fractions of ELF in children aged 3–15 years. These results should facilitate the comparison of BALF constituents in children of different age groups. Pediatr Pulmonol. 1996; 21:184–188. © 1996 Wiley-Liss, Inc.     

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

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