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Current management of acute bronchiolitis in Switzerland.

INTRODUCTION: Acute bronchiolitis is the most common lower respiratory tract infection in the first year of life. Current expert opinion and scientific data suggest that pharmaceutical agents have little impact on the natural course of the disease. METHODS: Postal questionnaires were sent to all Swiss paediatricians to assess their current practice for treating acute bronchiolitis in children. RESULTS: Of a total of 937 questionnaires, 541 (58%) were returned. Of the respondents, 422 (78%) treat children with acute bronchiolitis. Up to 99% of paediatricians used bronchodilators in the outpatient and inpatient management, either routinely (up to 62%) or occasionally (37%). Steroids were used by 41% of the respondents in outpatient management and by 57% in inpatient management. The paediatric respiratory physicians tended to use bronchodilators and corticosteroids less frequently than the general paediatricians. CONCLUSIONS: A wide variation in the treatment of bronchiolitis was noted. Despite lack of evidence of benefit most Swiss paediatricians use pharmaceutical agents in the management of acute bronchiolitis. In particular, bronchodilators and corticosteroids were used in inpatient management in Switzerland much more frequently than recently reported for Australian paediatricians. National guidelines could be helpful in reducing the variations in the management of acute bronchiolitis in our country.

Acute Disease↗

DNase treatment for atelectasis in infants with severe respiratory syncytial virus bronchiolitis.

Respiratory insufficiency due to respiratory syncytial virus (RSV) bronchiolitis is partly due to the abundance of thickened mucus and the inability to clear it from the airways. Mucus in RSV bronchiolitis contains necrotic inflammatory and epithelial cells. The viscoelastic properties of purulent airway secretions are largely due to the presence of highly polymerized deoxyribonucleic acid (DNA). Recombinant human deoxyribonuclease (rhDNase) is known to liquefy such mucus in patients with cystic fibrosis, whereas case reports described a beneficial effect in other respiratory disorders. The authors hypothesized that rhDNase would diminish atelectasis and mucus plugging in infants with severe RSV bronchiolitis. Two infants with RSV bronchiolitis with massive unilateral atelectasis in whom mechanical ventilation was imminent due to exhaustion, and three mechanically ventilated infants (two neonates, one with bronchopulmonary dysplasia) with RSV bronchiolitis with pneumonia received treatment with 2.5 mg nebulized rhDNase twice daily. Following administration of nebulized recombinant human deoxyribonuclease, clinical and radiological parameters improved quickly. Mechanical ventilation could be avoided in two infants while in three infants on artificial ventilation, clinical recovery started following the first dose of the drug. A therapeutic trial of recombinant human deoxyribonuclease may be an option in the treatment for atelectasis in severe or complicated respiratory syncytial virus bronchiolitis in infancy.

Administration, Inhalation↗

Typical findings for bronchiolitis in high resolution computed tomography.

High resolution computed tomography is a diagnostic modality of choice in imaging of interstitial lung diseases. HRCT enables visualization of the pathological findings invisible on plain radiographs and their evaluation at the level of the pulmonary lobule. The aim of the study was evaluation of typical HRCT findings in patients with bronchiolitis, and assessment of their usefulness in differential diagnosis. Tree in bud is a typical sign seen on HRCT sections in patients with bronchiolitis, resulting from filling the small centrilobular bronchioles with puss, mucus, granulomas or inflammatory cells. Material filling the bronchioles causes their obstruction resulting in the presence of air-trapping, visible on expiratory sections. Thickening of the bronchiolar walls and dilatation of the small bronchioles is also very often seen. Ground glass opacities and small nodules are also seen in some patients with bronchiolitis.

Angiography↗

[A bronchiolitis epidemic caused by respiratory syncytial viruses].

In the typical period of the year (autumn-winter 1986-1987) an outbreak of bronchiolitis in infants caused by respiratory syncytial virus (RSV) occurred. The acute course of the illness, a severe clinical picture, and a very fast spread of infection called for the very rapid techniques for detecting the etiological agent. Applying the direct immunofluorescent antibody test (DFTA) in samples of nasopharyngeal secretions, RSV was found to be responsible for the epidemic. Later the same samples of the material were inoculated into tissue cultures and RSV was isolated. Fourfold or higher titres of complement fixing antibodies in paired serum samples confirmed the infection with RSV. During the outbreak of bronchiolitis 72 children aged under 15 months (only one child was older than one year) were hospitalized. The majority of cases of RSV bronchiolitis was noticed in infants in the first six months of life (81.9%, chi 2 = 31.1, p less than 0.01). Boys against girls were in relation as 1.25:1. Because of the broncho-obstructive component of the illness, respiratory failure was the dominant sign in the clinical picture of bronchiolitis; 34.7% of the patients were afebrile, 16.7% were in the state of hyperpyrexy and 48.6% with temperature up to 38 degrees C. Oxygen and symptomatic therapy were the basic treatment. In severe cases corticosteroids and antibiotic were administered for a short time. The classical type of bronchiolitis in infancy as the most severe among acute infections of respiratory organs because of its poor prognosis at the very beginning and the long-term sequels is a serious medical problem. Emphasis is laid on the importance and usefulness of the virologic diagnosis, especially the application of rapid DFTA techniques in the acute stages of bronchiolitis caused by infections with respiratory syncytial virus during the epidemic occurrence of this agent.

Bronchiolitis, Viral↗

[Bronchiolitis obliterans in adults].

Bronchiols are defined as small upper airways with a diameter less than 2 mm. Two zones are described, membranous bronchioli with a continuous wall and respiratory bronchioli with a discontinuous wall. On the basis of pathology examinations, three disease processes can be recognized. In the first category, the initial inflammatory reaction in chronic obstructive bronchitis may spread to the bronchioli as can immune or infectious diseases resulting in bronchiolitis obliterans. Lesions originating conjointly in the bronchioli and alveoles form a second group including bronchiolitis obliterans organizing pneumoniae, the BOOP syndrome recently described. Histologically these disease entities show characteristic desquamation of the alveolar endothelium and a fibrinoid exudate. Hypoxaemia due to respiratory failure develops progressively and usually responds to corticosteroid therapy. In a third group, the disease is limited to the bronchioli alone with no large airway involvement. Chronic obstructive disease of the small airways has been described in smokers and people exposed to mineral dust. The clinical course often runs to classical chronic obstructive bronchopneumonia. Bronchiolitis obliterans itself, or constrictive bronchiolitis, is differentiated from BOOP due to the proliferative aspect within the lumen. No aetiological agent has been identified. The term bronchiolitis obliterans covers a wide range of more or less well identified entities which unfortunately have the common feature of generally poor response to treatment.

Adult↗

Risk factors for the development of obliterative bronchiolitis after lung transplantation.

BACKGROUND: Acute rejection has emerged as an important risk factor for obliterative bronchiolitis after lung transplantation. We performed a multivariate analysis to assess the impact of additional variables. METHODS: Seventy-four recipients (48 heart-lung, 18 single-lung, and 8 bilateral-lung recipients) who survived longer than 90 days and underwent transplantation more than 15 months before data analysis were included in this study. Several variables were entered into a Cox regression analysis to determine their association with the development of bronchiolitis obliterans syndrome. RESULTS: Bronchiolitis obliterans syndrome developed in 48 (65%) of 74 patients. Significant correlations were detected for acute rejection score, defined as the sum of pathologic grades of each separate acute rejection episode (p = 0.0004, likelihood ratio test value = 12.4) and for lymphocytic bronchiolitis (p = 0.03). In a bivariate model, episodes of organizing pneumonia and bacterial or fungal pneumonia significantly increased the likelihood ratio test value of the acute rejection score. The addition of the cytomegalovirus infection score, reflecting the frequency and severity of infection, to the combination of the acute rejection score and episodes of bacterial or fungal pneumonia resulted in a further significant increase in the likelihood ratio test value. Significant risk factors for moderate to severe stages of airflow limitation were at least one episode of acute rejection of grade > or = 2, younger recipient age, and any acute rejection episode 180 days or longer after transplantation. CONCLUSIONS: Increasing frequency and severity of acute rejection episodes are strongly associated with the development of bronchiolitis obliterans syndrome. Lymphocytic bronchiolitis appeared to be significant by univariate analysis, but in a two-risk factor model, it did not augment the influence of acute rejection. Organizing pneumonia, bacterial or fungal pneumonia, and increasing severity and frequency of cytomegalovirus infections potentiate the effect of acute rejection. Late episodes of acute rejection and younger recipient age increase the risk for development of advanced disease.

Adolescent↗

Bronchiolitis in children.

Bronchiolitis is an acute inflammation of the airways. In infancy, it usually results from viral infection, with RSV the most common agent. The clinical syndrome is characterized by symptoms of lower respiratory tract infection and obstruction. In most patients, the duration of illness is 1 week, but bronchiolitis can cause serious morbidity in patients with pre-existing cardiopulmonary disease. In addition, patients may be left with serious sequelae, including PBAR and OB. RSV causes direct damage to airways, but an exaggerated host immune response may contribute to the pathogenesis of airway obstruction in bronchiolitis. The mainstays of therapy include oxygen supplementation and fluid resuscitation, and other modalities remain controversial. There are no studies to support the use of corticosteroids alone in the treatment of bronchiolitis, but several recent reports demonstrate the value of bronchodilator therapy in some patients. Antiviral agents such as ribavirin show great promise in a therapy for bronchiolitis. In addition, ribavirin may modify some aspects of the immune response during acute infection with RSV, and therefore may play a role in the prevention of long-term sequelae.

Adrenal Cortex Hormones↗

Bronchiolitis obliterans organizing pneumonia.

Bronchiolar disorders can be divided into 2 general categories: (1) airway disorders (cellular bronchiolitis and obliterative bronchiolitis) and (2) parenchymal disorders (respiratory bronchiolitis-interstitial lung disease, which occurs in smokers and is treatable with smoking cessation or corticosteroid therapy, and bronchiolitis obliterans organizing pneumonia, an inflammatory lung disease simultaneously involving the terminal bronchioles and alveoli). This article reviews the clinical findings and therapeutic management of bronchiolitis obliterans organizing pneumonia.

Cryptogenic Organizing Pneumonia↗

Gelatinase B is required for alveolar bronchiolization after intratracheal bleomycin.

Increased expression of matrix metalloproteinases, particularly gelatinase B (MMP-9), has been described in the lungs in pulmonary fibrosis. Intratracheal bleomycin is often used experimentally to produce lesions resembling human fibrosing alveolitis. To assess the role of gelatinase B in bleomycin-induced fibrosing alveolitis, we instilled bleomycin intratracheally into gelatinase B-deficient mice and gelatinase B+/+ littermates. Twenty-one days after bleomycin the two groups of mice were indistinguishable in terms of pulmonary histology and total lung collagen and elastin. However, the lungs of gelatinase B-deficient mice showed minimal alveolar bronchiolization, whereas bronchiolization was prominent in the lungs of gelatinase B+/+ mice. Gelatinase B was identified immunohistochemically in terminal bronchiolar cells and bronchiolized cells 7 and 14 days after bleomycin in gelatinase B+/+ mice, and whole lung gelatinase B mRNA was increased at the same times. Many bronchiolized cells displayed Clara cell features by electron microscopy. Some bronchiolized cells stained with antibody to helix transcription factor 4, a factor associated with the ciliated cell phenotype. Thus, fibrosing alveolitis develops after intratracheal bleomycin irrespective of gelatinase B. However, gelatinase B is required for alveolar bronchiolization, perhaps by facilitating migration of Clara cells and other bronchiolar cells into the regions of alveolar injury.

Animals↗

Bronchoalveolar lavage in bronchiolitis obliterans organizing pneumonia primed by radiation therapy to the breast.

BACKGROUND: Growing evidence indicates that unilateral lung irradiation for breast cancer may "prime" the development of migratory lung infiltrates with histologic features of bronchiolitis obliterans organizing pneumonia. OBJECTIVE: Our purpose was to evaluate the cytologic and immunocytologic features of bronchoalveolar lavage in this condition. METHODS: We analyzed the profile bronchoalveolar lavage cell differentials and lymphocyte subpopulations of 11 women with bronchiolitis obliterans organizing pneumonia syndrome after radiation therapy for breast cancer in comparison to 9 healthy women. RESULTS: The bronchoalveolar lavage analysis demonstrated a significant increase in the percentage of lymphocytes (36.7% +/- 5.4% vs 8.6% +/- 1.1%, P =.0002), neutrophils (3.8% +/- 1.2% vs 0.6% +/- 0.2%, P =.005), eosinophils (2.4% +/- 1% vs 0.3% +/- 0.1%, P =.01), and mast cells (1.4% +/- 0.6% vs 0.1% +/- 0.02%, P =.05) with a significant decrease in the percentage of macrophages (56.1% +/- 6% vs 90.3% +/- 1.4%, P =.0002) in patients with bronchiolitis obliterans organizing pneumonia compared with the control subjects. The percentage of CD3(+) cells was significantly increased in patients with bronchiolitis obliterans organizing pneumonia (93.7% +/- 1.3% vs 70.9% +/- 4%, P =.0004), with a significant decrease in CD4(+) cells (32.7% +/- 4.7% vs 55.4% +/- 2. 6%, P =.002) and a significant increase in CD8(+) cells (61.2% +/- 4. 8% vs 37.5% +/- 2.9%, P =.003) in comparison to control subjects. The CD4/CD8 ratio was significantly reduced in patients with bronchiolitis obliterans organizing pneumonia compared with control subjects (0.6% +/- 0.1% vs 1.5% +/- 0.1%, P =.001). CONCLUSION: These data add to the view that unilateral lung irradiation for breast cancer may "prime" the development of a syndrome quite similar to idiopathic bronchiolitis obliterans organizing pneumonia.

Aged↗

Further observations on luminal deformity and stenosis of nonrespiratory bronchioles in pulmonary emphysema.

In an endeavour to elucidate the anatomical basis for the increased resistance to airflow which characterises the most peripheral conducting air passages in pulmonary emphysema, lumina of nonrespiratory bronchioles of lungs with mainly centrilobular disease were assessed for two- and three-dimensional features by: (1) determination of percentage conformity of the lumina of individual bronchioles in histological sections to hypothetical planes through cylinders (ie, ellipses with the same areas and circumferences), and (2) comparison of luminal areas at regular intervals along bronchiolar longitudinal axes. The lumina of most nonrespiratory bronchioles from normal lungs conformed closely to their respective ellipses, thus corroborating previous observations that they are normally cylindroid. In contrast, there was a substantial excess of plane section deformities in the lumina of nonrespiratory bronchioles from the emphysematous specimens. The incidence of stenotic bronchioles (by both diameter and area determinations) was also greatly increased in emphysema. Since there was a strong positive association between such stenotic lesions and bronchiolar deformity, the latter was concluded to be a major factor in bronchiolar restriction. Furthermore, these characteristics seemed to have three-dimensional expression, for the lumina of stenotic bronchioles in emphysema were irregular in a longitudinal fashion.

Bronchi↗

A quantitative study of stenosis in the respiratory bronchiole of the rat in NO2-induced emphysema.

Rats of similar age and size were exposed continuously to nitrogen dioxide (NO2) at a concentration of about 15 ppm in air for 1, 2, 3, and 4 wk and 2, 3, 4, 5, 7, 13, 15, and 17 months. Large increases in lung volume and lesions of the small airways and their epithelium and that of adjacent alveoli developed. The lesions in the terminal bronchioles involved hypersecretion and asggregation of cellular debris and free cells in their lumena. A calibrated grid fitted to an eyepiece was used to measure the diameters of all patent bronchioles at the proximal point of the first alveolar "break" in the respiratory bronchiole. The terminal bronchioles and their short respiratory bronchioles inthe NO2-exposed animals developed stenosis, which increased with time. The maximum change, occurring after 17 months of exposure, was a 45.6% reduction in bronchiolar diameter. Over-all constriction was underestimated because nonpatent sections of bronchioles were excluded The ratio of lung volume to bronchiolar diameter in exposed animals also increased with time as a result of the rising volume and the falling bronchiolar diameter. Probable are discussed.

Animals↗

Clara cell heterogeneity in differentiation: correlation with proliferation, ultrastructural composition, and cell position in the rat bronchiole.

Postnatal differentiation of nonciliated bronchiolar epithelial (Clara) cells occurs in a wave-like pattern beginning in the upper airways and ending in the terminal bronchiole. The heterogeneity of Clara cell differentiation observed during postnatal development in rats may be due to both cell turnover rate and cell position in the airways. To test the importance of these two factors in Clara cell differentiation, terminal bronchioles were examined in rats from gestational day 21 through postnatal day 100. The volume fraction of smooth endoplasmic reticulum (SER), a marker of differentiation, was seen to increase with age, while the epithelial cell labeling index of terminal bronchioles decreased over the same period. This represented a significant inverse correlation between SER volume density and cell proliferation rates (r2 = 0.80, P < 0.02). To evaluate the importance of cell position as a factor in cellular differentiation, the abundance of SER and secretory granules and the expression of cytochrome P450 isozyme 2B in Clara cells were examined along the entire length of the terminal bronchiole in animals 1, 21, and 100 days of age. For all three characteristics, Clara cells showed a similar degree of maturation from the proximal bronchiolar bifurcation to the bronchiole-alveolar duct junction (BADJ) (a span of approximately 35 cells). We conclude that during prenatal and postnatal bronchiolar development in rats: (1) the Clara cell is the most actively dividing cell type for the lower airways; (2) the stage of Clara cell differentiation is inversely related to Clara cell mitotic activity; and (3) the heterogeneity of Clara cell maturation and mitotic activity is not influenced by position within the terminal bronchiole.

Animals↗

Adult bronchiolitis. Evaluation by bronchoalveolar lavage and response to prednisone therapy.

Four adult patients with biopsy-proven bronchiolitis were identified and prospectively evaluated. Each patient presented with the rapid onset (weeks to months) of severe respiratory disease that was clinically distinct from asthma, chronic bronchitis, bronchiectasis, cystic fibrosis, and emphysema. Bronchiolitis patients were evaluated by pulmonary function testing and bronchoalveolar lavage (BAL) before and after two months of treatment with 1 mg/kg/day of prednisone. Initial BAL results of bronchiolitis patients were compared to those of cigarette smokers with chronic bronchitis (n = 4), asymptomatic cigarette smokers (n = 5), and normal nonsmoking volunteers (n = 5). Neutrophils comprised 53 +/- 13 percent of the cells recovered by BAL in bronchiolitis patients but only 3 +/- 2 percent of the cells in chronic bronchitis patients, 1.5 +/- 0.6 percent of the cells in asymptomatic smokers, and 0.3 +/- 0.3 percent of the cells in normal volunteers (p less than 0.01, all comparisons). Moreover, prednisone produced a striking decrease in lower respiratory tract neutrophils (53 +/- 13 percent to 8 +/- 3 percent, p less than 0.05) in all bronchiolitis patients while lung function either improved (two patients) or remained unchanged (two patients). These findings suggest a central role for the neutrophil in bronchiolitis and argue that BAL may be clinically useful in the diagnosis and management of these patients.

Adult↗

[Bronchiolitis obliterans in children]

OBJECTIVE: To review the literature on general aspects of bronchiolitis obliterans, with emphasis on childhood postinfectious bronchiolitis obliterans.METHODS: The most important publications on bronchiolitis obliterans were selected, using basically the Medline database (January of 1966 to September of 1999).RESULTS: This review is organized as follows: introduction, general aspects of bronchiolitis obliterans (terminology, histopathology and classification), and postinfectious bronchiolitis obliterans (etiological agents, clinical and radiological aspects, diagnosis and investigation, and treatment).COMMENTS: Bronchiolitis obliterans is a clinical syndrome wich is more common than previously believed in the pediatric population, thus deserving pediatricianś attention.

Journal Article↗

Small airways of the lung. The importance of understanding and assessing the function of pulmonary bronchioles.

Recent findings have emphasized the importance of the bronchiole to the function of the lung. The surface of the bronchiole differs from that of the alveolus. Rather than being covered by a thin coat of phospholipid, the surface is covered with cilia that are surrounded by a low-viscosity fluid. This permits the removal of foreign particles. Surface forces are important to the function of the bronchiole. The diameter of the bronchiole is a function of the volume of the lung. When the lung is partially collapsed, the bronchiole acts as a capillary tube and is readily obstructed by fluid. In chronic bronchitis, obstruction is related to narrowing by fibrosis and inflammation, alteration in the secretion, and loss of traction on the walls. Obstruction of the bronchiole by fluid in edema of the lung contributes to hypoxemia. Positive end expiratory pressure may prevent obstruction by increasing the bronchiolar diameter.

Airway Obstruction↗

Ion currents in smooth muscle cells from human small bronchioles: presence of an inward rectifier K+ current and three types of large conductance K+ channel.

Bronchoconstriction of small bronchioles plays a major role in the increase in airway resistance following agonist challenge. There is evidence that the airway smooth muscle (ASM) of small bronchioles differs functionally from that in larger airways. Little is known however about the electrophysiology of small bronchioles. Ion currents were therefore studied in airway smooth muscle cells freshly dissociated from human intralobular bronchioles, with a diameter between 0.3 and 1.0 mm. As previously reported for human large airways, the major outward current in these cells was due to activity of large conductance K+ (BK) channels, with a relatively minor component due to a voltage-gated delayed rectifier current (IDR), which was only observed in 30 % of cells. Three distinct types of iberiotoxin- and TEA-sensitive large conductance K+ channel contributed to large conductance K+ current (IBK). These included a highly voltage- and Ca2+-sensitive 200 pS channel previously reported in human large airways, and two smaller channels of 150 and 100 pS previously seen only in human fetal or cultured ASM. In contrast to large airways, ASM cells from bronchioles also demonstrated a voltage-gated inward rectifier current (IIR). IIR was activated by hyperpolarisation below the K+ equilibrium potential and could be blocked by submillimolar concentrations of Cs+ or Ba2+, and partially by physiological concentrations of Na+. Corresponding single channels with a conductance of 17 pS could also be recorded in the cell-attached configuration. A small voltage-independent current was also observed which was resistant to classic K+ and Cl- channel blockers but which could be abolished by replacement of Na+ with the impermeant cation N-methyl-D-glucamine (NMDG+). Corresponding non-selective single channels of 20 pS could be seen in inside-out mode. These results demonstrate that ASM from small bronchioles differs in terms of ion currents and channels from ASM derived from large airways, with possible implications for function.

Bronchi↗

Criteria for Safe Hospital Discharge in Bronchiolitis: A Systematic Review.

Bronchiolitis is the leading cause of hospital presentation and admission for infants in Australasia. We aimed to synthesise current evidence on the effect of discharge criteria for infants (aged <&#x2009;12&#x2009;months) who are presenting to or are admitted to hospital with bronchiolitis, to inform a binational guideline recommendation update. Systematic searches were conducted on MEDLINE, EMBASE, PubMed, Cochrane Library and CINAHL (last search 19 February 2025) for non-randomised studies evaluating hospital discharge criteria in bronchiolitis. The primary outcomes were length of stay (LOS) and readmission rates. The risk of bias (ROBINS-I) and certainty of the evidence (GRADE) were appraised, and findings were narratively synthesised. GRADE evidence-to-decision methodology, expert consensus voting and interest-holder consultation were used to finalise the recommendation update. Two retrospective observational studies were included (N&#x2009;=&#x2009;2697) (low to very low quality), reporting on unique discharge criteria. In both studies, use of the discharge criteria was associated with a significant reduction in LOS relative to alternative protocols. There was no significant difference in readmission rates observed in either study. There was low to very low certainty evidence across outcomes due to risk of bias, indirectness and imprecision. The review findings informed a recommendation update for safe discharge criteria in the 2025 Australasian Bronchiolitis Guideline update. Updated, prescriptive discharge criteria and flow chart were developed, covering clinical stability, oxygen saturation/support, feeding difficulties, caregiver confidence and education on deterioration, social factors and follow-up. The revised criteria provide clinicians with increased certainty in decision-making in bronchiolitis, albeit with further research needed.

Humans↗