Bronchiolitis Group Research Articles

Lipopolysaccharide hyporesponsiveness as a risk factor for intensive care unit hospitalization in infants with respiratory syncitial virus bronchiolitis

Factors such as genetic heterogeneity in the immune response contribute to respiratory syncytial virus (RSV) bronchiolitis severity. Such heterogeneity may manifest by an aberrant proliferation of phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) in response to lipopolysaccharide (LPS). The proliferation of PBMC was analysed in 52 infants: 21 ambulatory infants with mild RSV bronchiolitis (group I), 26 hospitalized infants with RSV bronchiolitis on ward (group II) and five intensive care unit (ICU) hospitalized infants (group III). Proliferation was analysed in response to negative control, PHA (LPS) and LPS/PHA. The TLR4 mutations were genotyped using reverse-transcriptase-polymerase chain reaction. The optical density (OD) post-LPS/PHA of group II (1.27 +/- 0.63) was significantly higher than group II (0.65 +/- 0.38, P = 0.005) or group I (0.63 +/- 0.33, P = 0.003), suggesting hyporesponsiveness to the LPS attenuation effect. None of the ICU hospitalized infants demonstrated OD readings post-LPS/PHA under the 0.75 threshold as opposed to group I (67% under 0.75) and group II (69%) (P < 0.05). The responses to negative-control, LPS and PHA stimulation alone were similar across groups. The presence of TLR4 mutations (Asp299Gly and Thr399Ile) were associated with severe RSV bronchiolitis and were significantly over-represented in groups II and III. These findings suggest that impairments of PBMC function manifested by hyporesponsiveness to LPS as well as the presence of TLR4 mutations are associated with an increased risk for more severe RSV bronchiolitis in previously healthy infants. A certain threshold of LPS hyporesponsiveness may have a very high negative predictive value for ICU hospitalization, even better than the determination of known TLR4 mutations for this purpose.

Bronchoalveolar lavage eosinophil cationic protein and interleukin‐8 levels in acute asthma and acute bronchiolitis

In this study, we measured the levels of eosinophil cationic protein (ECP) and interleukin (IL)-8 in bronchoalveolar lavage (BAL) fluid from patients with acute asthma and acute bronchiolitis, to determine any similarities or dissimilarities in the profiles of these biochemical markers in the two diseases. BAL fluids were obtained from children with acute asthma (n=16), infants with acute bronchiolitis caused by respiratory syncytial virus (n=18), and control subjects (n=14). Children with asthma were selected to be free of viral infection. BAL cell counts and differentials were determined, and ECP and IL-8 levels were measured by radioimmunoassay and ELISA, respectively. ECP levels in BAL fluids were significantly higher in the asthma group than in the bronchiolitis (P<0.01) or control (P<0.0001) groups. However, IL-8 levels were significantly higher in the bronchiolitis group than in the asthma (P<0.01) or control (P<0.001) groups. IL-8 levels in the asthma group and ECP levels in the bronchiolitis group were similar to those of the control group. This difference in profiles of ECP and IL-8 in acute asthma and acute bronchiolitis, together with a different inflammatory cell pattern, suggests that the nature of the inflammatory process within the lower respiratory tract may be distinctive in these two diseases.

Respiratory repercussions in adults with a history of infantile bronchiolitis

Viral bronchiolitis in infancy has been identified in previous studies as a potential precursor to the development of lower respiratory tract illness in later childhood and beyond. To evaluate the long-term respiratory repercussions of acute infantile viral bronchiolitis. We studied 71 individuals aged 19 to 24 years with a history of a viral bronchiolitis in infancy and 32 controls. All participants underwent the following evaluation: medical history, forced spirometry, methacholine challenge, and skin prick testing. The bronchiolitis group had a higher prevalence of respiratory symptoms (P = .03) and bronchial hyperresponsiveness (P = .003) than controls. The bronchiolitis group also had a lower peak expiratory flow rate (P = .02). Skin prick test responses were similar in both groups. The findings from this study support and extend those from previous studies by suggesting that viral bronchiolitis may be a predisposing factor for lower respiratorytract problems in young adulthood.

Asthma and Lung Function 20 Years After Wheezing in Infancy

To determine the outcome until adulthood after wheezing in infancy, compared with pneumonia in infancy and with controls. An 18- to-20-year prospective cohort study. Pediatric department at a university hospital, providing primary hospital care for a defined population. Patients Fifty-four children hospitalized for bronchiolitis and 34 for pneumonia at younger than 2 years, and 45 controls with no early-life wheezing or hospitalization, were studied at median age 19 years. A questionnaire on asthma symptoms and medication, physical examination, flow volume spirometry (FVS), methacholine inhalation challenge (MIC), home peak expiratory flow (PEF) monitoring, and skin prick testing (SPT) to common inhalant allergens. The 2 asthma definitions were physician-diagnosed asthma and previously diagnosed asthma with recent asthmatic symptoms (physician-diagnosed asthma included). By the 2 definitions, asthma was present in 30% (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.12-10.10) and in 41% (OR 1.38; 95% CI, 0.37-5.21) in the bronchiolitis group, in 15% (OR, 5.50; 95% CI, 1.87-16.14) and in 24% (OR, 2.07; 95% CI, 0.59-7.22) in the pneumonia group, and in 11% in the control group. After bronchiolitis, the FVS values were forced vital capacity (FVC), 108% (SD, 13%) of predicted; forced expiratory volume in 1 second, 98% (SD, 12%); forced expiratory volume in 1 second divided by FVC, 91% (SD, 7.6%); midexpiratory flow at 50% of the FVC, 74% (SD, 19%); and midexpiratory flow at 25% of the FVC, 74% (SD, 22%). Bronchial reactivity by MIC was present in 25 (48%) of 52 subjects in the bronchiolitis group, in 13 (42%) of 31 in the pneumonia group, and in 14 (32%) of 44 in the control group. The prevalence of atopy (positive SPTs) was 48% to 63% in the 3 groups. In a logistic regression adjusted for atopy and smoking, infantile bronchiolitis was an independent risk factor for asthma by both definitions. The increased risk for asthma persists until adulthood after bronchiolitis in infancy.

Does bronchiolitis caused by RSV predispose to atopic asthma?

Based on results from the Tucson Children's Respiratory Study, three different forms of wheezing in children have been proposed: transient infant wheezers, non-atopic wheezers, and atopic wheezers (i.e. children with atopic asthma with IgE antibodies to environmental allergens). All controlled studies of children with RSV bronchiolitis in infancy have revealed that wheezing can continue for varying lengths of time after the infection has subsided. The pathophysiology of this disorder remains to be clarified. Is this wheezing a transient and benign condition, or is it non-atopic, in which case the long-term prognosis is good, or is it a marker for atopic asthma? We have followed prospectively 47 children hospitalised with RSV bronchiolitis and 93 non-bronchiolitis matched controls. The results of follow-up examinations at age 3 and 7 years showed that the incidence of asthma—in children with or without IgE antibodies—was significantly increased in the RSV bronchiolitis group compared to the control group. We observed similar results in a recent follow-up study of these same children at age 13. Our results suggest that infants with RSV bronchiolitis severe enough to cause hospitalisation are at risk for atopic asthma at age 13.

Association between Common Toll‐Like Receptor 4 Mutations and Severe Respiratory Syncytial Virus Disease

The clinical spectrum of respiratory syncytial virus (RSV) bronchiolitis in previously healthy infants is extremely variable. Thus, it is likely that factors such as genetic heterogeneity contribute to disease severity. Toll-like receptor 4 (TLR4) and CD14 are part of a receptor complex involved in the innate immune response to RSV. The association of the TLR4 mutations (Asp299Gly and Thr399Ile) and the CD14/-159 polymorphism were analyzed in 99 infants hospitalized with severe RSV bronchiolitis (group I). Eighty-two ambulatory infants with mild RSV bronchiolitis (group II) and 90 healthy adults (group III) composed the 2 control groups. The TLR4 mutations and the CD14/-159 polymorphism were genotyped by use of reverse-transcriptase polymerase chain reaction and restriction fragment-length polymorphism analysis, respectively. Each of the TLR4 mutations, either alone or in cosegregation, were associated with severe RSV bronchiolitis: the Asp299Gly and Thr399Ile mutations were significantly overrepresented in group I, compared with groups II and III. No association between the CD14/-159 polymorphism and RSV bronchiolitis was found. These findings suggest that TLR4 mutations, but not the CD14/-159 polymorphism, are associated with an increased risk of severe RSV bronchiolitis in previously healthy infants.

Bronchoalveolar lavage cytokine profiles in acute asthma and acute bronchiolitis

Background: The pathogenetic basis for the relationship between acute bronchiolitis and asthma has not yet been completely elucidated. Objective: The aim of this study was to compare these 2 diseases in terms of their patterns of airway cytokine response (TH1 or TH2). Methods: By using a bronchoalveolar lavage (BAL) technique, this study investigated the cytokine levels of BAL fluid in children with acute asthma who had no identifiable respiratory syncytial virus (RSV) infection (n = 18) and in infants with acute bronchiolitis caused by RSV (n = 22). Comparisons were made with normal control subjects (n = 14). IFN-γ (TH1) and IL-4 and IL-5 (TH2) levels were measured in concentrated BAL fluids by means of ELISA. Results: The IL-5 level (P < .001) and IL-5/IFN-γ ratio (P < .001) were significantly increased in the asthmatic group with no identifiable RSV infection and in the RSV-induced bronchiolitis group compared with values in the control group. When infants in the bronchiolitis group were divided into eosinophil-positive and eosinophil-negative subgroups, the eosinophil-positive subgroup had significantly increased IL-5 levels (P < .001) and IL-5/IFN-γ ratios (P < .01) compared with those in the control group, but similar cytokine responses were not induced in the eosinophil-negative subgroup. The percentage of BAL eosinophils correlated significantly with levels of BAL IL-5 in both the asthma group (r = 0.80, P = .000) and the bronchiol-itis group (r = 0.82, P = .000). Conclusions: These findings suggest that a subgroup of the RSV-induced bronchiolitis group results in a TH2-type response, and this could provide a valuable framework to explain the link between RSV-induced bronchiolitis and asthma. (J Allergy Clin Immunol 2003;112:64-71.)

Moderate local and systemic respiratory syncytial virus-specific T-cell responses upon mild or subclinical RSV infection.

Respiratory syncytial virus (RSV) infections are a major cause of severe respiratory disease in infants. It has been shown that there is an increased frequency of childhood wheezing in ex-bronchiolitic preteen children. This was postulated to be mediated by a vigorous virus-specific Th2 response influencing the further development of the immune system. Little is known about the possible role of the immune response to clinically mild RSV infections in this respect. We have studied the RSV-specific cellular immune response in infants with a laboratory-confirmed RSV upper respiratory tract infection (URTI; n = 13, mean age 12 months, range 2-22 months) in comparison with infants with non-RSV mediated URTI (n = 9, mean age 9.3 months, range 4-18 months) or infants with severe RSV bronchiolitis (n = 11, mean age 2.3 months, range 1-6 months). RSV-specific cytokine-producing cells were enumerated using the ELISPOT method in peripheral blood mononuclear cells and nasal brush T-cells, collected during the acute and convalescent phase of the infection. Mixed Th1 (IFN-gamma) and Th2 (IL-4 and IL-13) responses were detected in all three groups. Frequencies of RSV-specific T-cells were lower in both URTI groups than in the RSV bronchiolitis group, and not significantly different between the RSV URTI and the non-RSV URTI group. The absence of vigorous virus-specific Th2 responses upon mild RSV infection does not support the hypothesis that these infections influence the development of the immune system and that they predispose for the development of atopic disease.

A cohort of children hospitalised with acute RSV bronchiolitis: impact on later respiratory disease.

This paper reviews the results from a cohort study in which 47 children hospitalised with respiratory syncytial virus (RSV) bronchiolitis and their 93 controls, matched for age, sex and place of living, were prospectively followed-up at the mean ages of 1, 3 and 7.5. Asthma was significantly more common in the RSV bronchiolitis group at all times. Asthma during the year prior to follow-up at age 7.5 was seen in 23% of the RSV children and in 2% of the controls (P < 0.001). Allergic sensitisation was found in 41% of the RSV children and in 22% of the controls (P = 0.039). When comparing these results with findings from other studies it is obvious that the rate of asthma and other bronchial obstructive symptoms are increased after RSV bronchiolitis but the various results concerning allergic sensitisation are not conclusive. Prospective studies are needed with some kind of randomised intervention against RSV before the mechanisms behind the post-bronchiolitic symptoms and the possibly increased risk for IgE mediated allergy can be settled.

Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity.

This study was designed to collect data on the prevalence of respiratory syncytial virus (RSV) infection in Italy in infants hospitalized for lower respiratory tract infections, and to evaluate which of the recognized risk factors might be associated with disease severity. Thirty-two centers throughout Italy participated in the study. Over a 6-month period (November 1,1999 to April 30, 2000), we evaluated all children < 2 years of age hospitalized for lower respiratory tract infections. All subjects were tested for RSV within 24 hr of hospitalization by using an immuno-enzymatic diagnostic test (Abbott Testpack, RSV). Logistic regression was used to identify the factors that might be associated with more severe disease or could increase the likelihood of RSV positivity in hospitalized infants. Out of a total of 1,232 children enrolled, 40.6% were found to be RSV-positive (RSV+). The peak of the RSV epidemic occurred in February, while the lowest prevalence of RSV positivity was seen in November (P < 0.05). A high proportion of study subjects had low birth weight and low gestational age. The clinical diagnosis at hospitalization was bronchiolitis in 66.7%, pneumonia in 15.3%, and wheezy bronchitis in 18.1%. In the bronchiolitis group, a higher prevalence of RSV+ was found in patients with gestational age <or= 33 weeks or 34-35 weeks, as compared to those with a gestational age >or= 36 weeks (P < 0.04). No differences were found in the proportion of RSV+ patients in the three gestational age subgroups with pneumonia and wheezy bronchitis (P > 0.05, each comparison). Independent of the clinical diagnosis at admission, RSV infection was associated with more severe respiratory impairment. Environmental smoke exposure was higher in subjects with bronchiolitis than in those with wheezy bronchitis (P < 0.04), and RSV+ was positively related with the birth order (P < 0.05). The presence of older siblings and birth order plays an important role in RSV infection. The collected data show that, in Italy, RSV is an important cause of lower respiratory tract infection in infants. Gestational age, birth order, birth weight, and exposure to tobacco smoke affected the prevalence and severity of RSV-related lower respiratory tract disease.

Bronchoalveolar lavage cellular composition in acute asthma and acute bronchiolitis

Objective: To compare cellular inflammation in the airways between acute bronchiolitis and asthma. Study design: Using a bronchoalveolar lavage with flexible bronchoscopy procedure, we investigated the cellular constituents of BAL fluid in children with acute exacerbation of asthma (n = 18) and infants with acute bronchiolitis caused by respiratory syncytial virus (n = 20). These results were compared with those of healthy control subjects (n = 14). Results: Total lavage fluid recovered was similar in all groups. The total cell numbers were highest in the bronchiolitis group. The BAL cellular profile in the asthma group was characterized by a higher median (interquartile range) ratio of eosinophils (2.4% [1.6%-9.5%]; P <.01) than in the bronchiolitis group (0% [0%-0%]) or the control group (0% [0%-0%]). Neutrophil ratio was higher in the bronchiolitis group (40.0% [26.5%-50.0%]; P <.01), with no difference found between the asthma group (3.3% [2.0%-7.9%]) and the control group (2.0% [0.8%-5.5%]). Conclusions: Asthma and acute bronchiolitis are characterized by an elevated cellular percentage of eosinophils and neutrophils, respectively, in bronchoalveolar lavage fluid. (J Pediatr 2000;137:517-22)

Feeding efficiency and respiratory integration in infants with acute viral bronchiolitis

Objective: To examine the effects of bronchiolitis on feeding efficiency and respiratory integration. Study design: We studied 21 infants with bronchiolitis and 21 bottle-fed healthy infants who formed a comparison group. Repeat evaluations of half the bronchiolitis group were performed during recovery. During each feeding study we measured the duration and frequency of sucking, the frequency of single and multiple swallows, the respiratory rate, the postswallow respiratory direction, and the suck and swallow volumes. Results: The infants with bronchiolitis devoted significantly less time to sucking than their healthy peers (P <.05), and the mean suck volume was reduced. Although the frequency of swallowing was slightly higher, the volume of milk consumed per swallow was almost half the amount consumed by the comparison group (P <.01). Coordination of breathing with swallowing was also less effective (P <.01). Conclusion: Although most aspects of feeding are less efficient during periods of respiratory illness, others are preserved or recover rapidly. Coordination of breathing during feeding is also significantly impaired. (J Pediatr 2000;137:523-6)

Long‐term effects of respiratory syncytial virus (RSV) bronchiolitis in infants and young children: a quantitative review

One of the major questions regarding long‐term side effects of bronchiolitis by respiratory syncytial virus (RSV) is whether or not it induces asthma in later life. In this quantitative review, the data of 10 controlled studies are analysed. Methods: Follow‐up studies of RSV bronchiolitis published between January 1978 and December 1998 were identified through a MEDLINE search. Studies were selected if (i) postnatal age at the time of the inital illness was below 12 mo, (ii) all children were hospitalized for RSV bronchiolitis, (iii) the diagnosis RSV was virologically confirmed in all cases, and (iv) a control group was used. Results: Six studies met all selection criteria. Up to 5 y of follow‐up after RSV bronchiolitis in infancy, 40% of children reported wheezing as compared to only 11% in the control group (p &lt; 0.001). Between 5 and 10 y of follow‐up 22% of the bronchiolitis group reported wheezing against 10% of the control group (p= 0.19). The incidence of recurrent wheezing as defined by three or more wheezing episodes also decreased with increasing years of follow‐up: at 5 or more years of follow‐up the difference between the RSV group and the control group was no longer significant. Furthermore, the presence of either a personal and/or a family history of either atopy and/or asthma did not differ between the two groups.Conclusions: Wheezing is common after RSV bronchiolitis in infancy. It may persist for 5 y of follow‐up. However, no significant difference between the RSV bronchiolitis and the control group was observed regarding recurrent wheezing by 5 y of follow‐up. No significant difference between the RSV bronchiolitis and the control group were found regarding a personal history of atopy, a family history of atopy and/or asthma. Therefore it seems unlikely that RSV bronchiolitis is a cause of atopic asthma in later life.

Atopy and Pulmonary Function Abnormalities in Children with a History of Acute Bronchiolitis

To assess the relationship between acute viral bronchiolitis and subsequent development of asthma, we studied retrospectively 97 index children, aged between 9 and 14 years, and 52 controls. The bronchiolitis group showed significantly lower values for mean expiratory flow at 50% of vital capacity (MEF50), higher incidence of atopy, and were more sensitive to methacholine than were controls, even if they had not shown recurrent wheezing episodes. It is suggested that an increased incidence of atopy, bronchial hyperresponsive-ness, and reduced expiratory flows may be detectable in children with a history of acute bronchiolitis, regardless of the fact that they did not develop subsequent clinical symptoms suggestive of bronchial asthma.

Long-term effects of respiratory syncytial virus (RSV) bronchiolitis in infants and young children: a quantitative review.

One of the major questions regarding long-term side effects of bronchiolitis by respiratory syncytial virus (RSV) is whether or not it induces asthma in later life. In this quantitative review, the data of 10 controlled studies are analysed. Follow-up studies of RSV bronchiolitis published between January 1978 and December 1998 were identified through a MEDLINE search. Studies were selected if (i) postnatal age at the time of the initial illness was below 12 mo, (ii) all children were hospitalized for RSV bronchiolitis, (iii) the diagnosis RSV was virologically confirmed in all cases, and (iv) a control group was used. Six studies met all selection criteria. Up to 5 y of follow-up after RSV bronchiolitis in infancy, 40% of children reported wheezing as compared to only 11% in the control group (p <0.001). Between 5 and 10 y of follow-up 22% of the bronchiolitis group reported wheezing against 10% of the control group (p = 0.19). The incidence of recurrent wheezing as defined by three or more wheezing episodes also decreased with increasing years of follow-up: at 5 or more years of follow-up the difference between the RSV group and the control group was no longer significant. Furthermore, the presence of either a personal and/or a family history of either atopy and/or asthma did not differ between the two groups. Wheezing is common after RSV bronchiolitis in infancy. It may persist for > or = 5 y of follow-up. However, no significant difference between the RSV bronchiolitis and the control group was observed regarding recurrent wheezing by 5 y of follow-up. No significant difference between the RSV bronchiolitis and the control group were found regarding a personal history of atopy, a family history of atopy and/or asthma. Therefore it seems unlikely that RSV bronchiolitis is a cause of atopic asthma in later life.

Viral aetiology and epidemiology of acute respiratory infections in hospitalized Saudi children.

A total of 1429 Saudi children of either sex and under 5 years of age who were admitted to King Khalid University Hospital, Riyadh during a three year period (April 1993–March 1996) with complaints suggestive of acute respiratory tract infections (ARTI) were investigated for viral aetiology of the infection. Viruses could be detected in 522 (37 per cent) cases with respiratory syncytial virus (RSV) the most commonly detected (79 per cent) followed by parainfluenza type 3 (8 per cent). Detection of influenza A, B and adenoviruses accounted for 6 per cent, 3 per cent and 2 per cent respectively. Except for parainfluenza virus type 3 the peak of activity of the respiratory viruses was during the winter months (October–February). Parainfluenza virus type 3 could be detected all year round but epidemics can occur in the hottest months of the year (June–August) when the temperature can exceed 40°C. Association between clinical manifestation, type of causative agent, and age was evaluated in 137 infected Saudi children in the first year of the study (April 1993–March 1994). The majority of our cases presented with bronchiolltis (58 per cent) while only 26 per cent had bronchopneumonla. There was a significant association between bronchiolitis and lower age groups (0–6 months), with RSV as the major causative agent of bronchiolitis cases (88 per cent).

Surfactant abnormalities in infants with severe viral bronchiolitis.

To determine whether abnormalities of pulmonary surfactant occur in infants with acute viral bronchiolitis, surfactant indices were measured in lung lavage fluid from 12 infants with severe bronchiolitis and eight infants without lung disease. Compared with controls, the bronchiolitis group showed deficiency of surfactant protein A (1.02 v 14.4 micrograms/ml) and disaturated phosphatidylcholine (35 v 1060 micrograms/ml) which resolved as the disease improved. Surfactant functional activity was also impaired (minimum surface tension 22 v 17 mN/m). These findings indicate that surfactant abnormalities occur in bronchiolitis, and may represent one of the pathophysiological mechanisms causing airway obstruction.

Bronchial Asthma and Hyperreactivity After Early Childhood Bronchiolitis or Pneumonia

To determine the infantile risk factors and long-term outcome up to 8 to 10 years of age for bronchial asthma and hyperreactivity in children with early-childhood bronchiolitis or pneumonia. Prospective follow-up of three groups of children. University hospital providing primary hospital care and outpatient consultations for all pediatric patients in a defined area. None. The study groups consisted of 62 children with early-childhood bronchiolitis, 29 children with early-childhood pneumonia with no wheezing, and 52 control children. Infantile risk factors were prospectively registered until 2 years of age. Clinical examination, performed 7 to 8 years later, included recording of atopic and asthmatic symptoms from the preceding 12 months. The methacholine inhalation challenge test was used to assess bronchial hyperreactivity, and mean midexpiratory flow results were used to assess bronchial obstruction. Bronchial asthma was present in nine (15%) of the 62 children from the bronchiolitis group, compared with 7% in the pneumonia group and 2% in the control group. Bronchial hyperreactivity indicated by methacholine inhalation challenge was far more common; it was present in 62% of the bronchiolitis group and in 45% of the pneumonia group. Both groups differed significantly from the control group. Decreased mean midexpiratory flow values were observed in 29% and 21% of the bronchiolitis and pneumonia groups, respectively. All 10 asthmatic patients had bronchial hyperreactivity, but only 20% of hyperreactive children had asthma. An analysis of infantile risk factors disclosed only one, an early onset of wheezing, with a significant effect on bronchial hyperreactivity at school age. Elevated IgE values measured during infancy were associated with the development of clinical asthma. The risk of bronchial asthma was increased after infantile bronchiolitis. Moreover, bronchial hyperreactivity was increased after both infantile bronchiolitis and pneumonia. Methacholine inhalation challenge was a sensitive but nonspecific test for diagnosing bronchial asthma. Both bronchiolitis and pneumonia resulting in hospitalization in early childhood distinguish a group of children with an increased risk for long-term lung function abnormalities and pulmonary illnesses.

Bronchiolitis in Adults: A Reversible Cause of Airway Obstruction Associated with Airway Neutrophils and Neutrophil Products

In the past 4 yr, 16 adult patients were identified who had accelerated onset of a severe respiratory disorder (usually obstructive in nature) that was clinically distinct from the more commonly encountered chronic obstructive disorders (e.g., chronic bronchitis, emphysema, asthma, bronchiectasis, cystic fibrosis, and alpha 1-antitrypsin deficiency). These patients, termed patients with "bronchiolitis," underwent pulmonary function testing, bronchoscopy with bronchoalveolar lavage (BAL), and open lung biopsy. Although lung biopsy findings varied somewhat among the patients, each biopsy contained a prominent component of bronchiolitis. Pulmonary function testing and BAL were also repeated after 3 months of treatment with oral prednisone (1 mg/kg/day). Initial BAL neutrophil percentages were significantly higher in the bronchiolitis group (54 +/- 10%) than in smokers with chronic bronchitis (3.9 +/- 1.0%) or in normal nonsmoking volunteers (0.8 +/- 0.5%) (p less than 0.01, both comparisons). Eleven of 15 patients with bronchiolitis had significant improvement (greater than or equal to 15% increase in FEV1) in their lung function after prednisone treatment. Furthermore, this "responder" subgroup had a significant reduction in BAL neutrophil percentages after treatment with prednisone (46 +/- 15% to 6 +/- 3%, p less than 0.05). Finally, the neutrophil products collagenase and myeloperoxidase were detected in the BAL fluid of patients with bronchiolitis. These findings suggest a central role for the neutrophil in the pathogenesis of bronchiolitis and emphasize the utility of BAL in the identification of these patients.

Bronchial reactivity in infants in acute respiratory failure with viral bronchiolitis.

Airway reactivity and the effects of bronchodilators in infants are controversial. We studied the response to bronchodilator treatment in 14 mechanically ventilated infants (mean age, 2.74 months; range, 0.6-5.9) in respiratory failure caused by respiratory syncytial virus (RSV)-associated bronchiolitis. Sixteen infants without lung disease, undergoing elective surgery, provided normal values. Maximum expiratory deflation flow-volume (DFV) curves were produced by manual inflation of the lungs with an anesthesia bag to a predetermined static airway pressure followed by rapid deflation with a negative airway pressure before and after administration of bronchodilator. At baseline, the bronchiolitis group had a forced vital capacity (FVC) of 34.5 +/- 3.6 ml/kg compared with 41.8 +/- 1.5 ml/kg in the normal group; maximum expiratory flow rate at 25% of FVC (MEF25) was 10.2 +/- 2.0 ml/kg/s compared with 27.3 +/- 2.0 ml/kg/s in the normal group. The clinical and radiologic impression was severe lower airway obstruction and air trapping. After administration of bronchodilator, FVC did not increase significantly, but MEF25isov increased by over 30% in 13 of 14 infants. Mean MEF25 increased by 148 +/- 43.2% to 21.7 +/- 3.9 ml/kg/s (P less than 0.02). These findings indicate that during the acute phase of severe RSV-positive bronchiolitis most infants have airway reactivity that responds positively to bronchodilator treatment.