Bronchiolitis and Bronchiolar Disorders.

Bronchioles are noncartilaginous small airways with internal diameter of 2 mm or less, located from approximately the eighth generation of purely air conducting airways (membranous bronchioles) down to the terminal bronchioles (the smallest airways without alveoli) and respiratory bronchioles (which communicate directly with alveolar ducts and are in the range of 0.5 mm or less in diameter). Bronchiolar injury, inflammation, and fibrosis may occur in myriad disorders including connective tissue diseases, inflammatory bowel diseases, lung transplant allograft rejection, graft versus host disease in allogeneic stem cell recipients, neuroendocrine cell hyperplasia, infections, drug toxicity (e.g., penicillamine, busulfan), inhalation injury (e.g., cigarette smoke, nylon flock, mineral dusts, hard metals, Sauropus androgynous); idiopathic, common variable immunodeficiency disorder, and a host of other disorders or insults. The spectrum of bronchiolar disorders is wide, ranging from asymptomatic to fatal obliterative bronchiolitis. In this review, we discuss the salient clinical, radiographic, and histological features of these diverse bronchiolar disorders, and discuss a management approach.

Lung Ultrasound and Clinical Progression of Acute Bronchiolitis: A Prospective Observational Single-Center Study.

Background and Objectives: Recent literature suggests that lung ultrasound might have a role in the diagnosis and management of bronchiolitis. The aim of the study is to evaluate the relationship between an ultrasound score and the clinical progression of bronchiolitis: need for supplemental oxygen, duration of oxygen therapy and hospital stay. Materials and Methods: This was a prospective observational single-center study, conducted in a pediatric unit during the 2017-2018 epidemic periods. All consecutive patients admitted with clinical signs of acute bronchiolitis, but without the need for supplemental oxygen, underwent a lung ultrasound in the first 24 h of hospital care. The lung involvement was graded based on the ultrasound score. During clinical progression, need for supplemental oxygen, duration of oxygen therapy and duration of hospital stay were recorded. Results: The final analysis included 83 patients, with a mean age of 4.5 ± 4.1 months. The lung ultrasound score in patients that required supplemental oxygen during hospitalization was 4.5 ± 1.7 (range: 2.0-8.0), different from the one of the not supplemented infants (2.5 ± 1.8; range: 0.0-6.0; p < 0.001). Ultrasound score was associated with the need for supplemental oxygen (OR = 2.2; 95% CI = 1.5-3.3; p < 0.0001). Duration of oxygen therapy was not associated with LUS score (p > 0.05). Length of hospital stay (coef. = 0.5; 95% CI = 0.2-0.7; p < 0.0001) correlates with LUS score. Conclusion: Lung ultrasound score correlates with the need of supplemental oxygen and length of hospital stay in infants with acute bronchiolitis.

Validation of a scale to assess the severity of bronchiolitis in a population of hospitalized infants.

BACKGROUND: Although assessment of the severity of bronchiolitis using severity scores is important both in daily practice and as an outcome measure in clinical trials, many of these scores have not been formally validated or have been only partially validated. METHODS: We conducted a prospective cohort study on a sample of children diagnosed with bronchiolitis. Two physicians independently assessed all of the children on the modified Wood's Clinical Asthma Score (M-WCAS) and on the Tal et al. severity score and collected the information required to assess the criterion validity, construct validity, inter-rater agreement, sensitivity to change, and usability of the M-WCAS. RESULTS: The median (interquartilic range [IQR]) of the age of the 54 patients included in the study was 5 (2-9) months. Thirty (55.6%) of the patients were males and 24 (44.4%) were female. The scores of the M-WCAS correlated positively with the scores of the Tal et al. severity score (ρ = 0.761, p < 0.001). The scores of the M-WCAS in patients who required subsequent admission to the PICU were significantly higher than those in patients who required admission only to the pediatric medical floor (PMF) [4.5 (3.6-5.2) vs. 2.5 (1.5-2.5), p < 0.001]. The inter-rater agreement for the raters was found to be κ = 0.897 (p < 0.001), 95% CI (0.699-1.000). The scores of the M-WCAS in patients at admission to the PMF were significantly higher than those obtained immediately before discharge from the hospital [2.5 (1.9-2.5) vs. 1.0 (0.5-1.6), p < 0.001). CONCLUSIONS: Our results suggest that the M-WCAS severity score has adequate criterion validity, adequate construct validity, adequate inter-rater agreement, adequate sensitivity to change, and appropriate usability for infants hospitalized for acute bronchiolitis.

Lymphocytic interstitial pneumonia and other benign lymphoid disorders.

Nonneoplastic pulmonary lymphoid disorders consist of a complex spectrum of diseases for pathologists and pulmonologists alike. Advances in our understanding of these disorders in recent years have led to revisions in the classification scheme. This review summarizes the clinicoradiological and pathological features of several benign pulmonary lymphoid disorders as well as the current knowledge regarding their pathogenesis. The disorders discussed include lymphocytic interstitial pneumonitis, follicular bronchiolitis, nodular lymphoid hyperplasia, inflammatory pseudotumor, Castleman disease, immunoglobulin G4-related disease in the lung, and posttransplant lymphoproliferative disease.

[Bronchiolitis. Part 1--anatomic features, classification, clinical presentation and imaging]. / Bronchiolitis. Teil 1--Anatomische Grundlagen, Klassifikation, klinische Präsentation und Bildgebung.

The term "bronchiolitis" refers to a broad spectrum of common conditions related to the small airways associated with a miscellaneous aetiology, histology, clinical features and course. Due to their variability, bronchiolar disorders are generally difficult to diagnose. History (smoking, collagen vascular disease, inhalational injury, medication usage, and organ transplant) may point towards a bronchiolar process. In addition, signs of systemic and pulmonary infection and evidence of air trapping may provide diagnostic hints. Although clinical presentation, physical examination, pulmonary function tests (obstructive ventilatory defect), and plain chest radiographs may demonstrate abnormalities suggesting small airways involvement, they are often non-specific and rarely diagnostic. In contrast, the high-resolution CT (HR-CT) scanning of the chest provides three distinct HR-CT patterns that assist in the diagnosis and differential diagnosis of bronchiolar conditions: (i) a tree-in-bud pattern, (ii) ill-defined centrilobular ground-glass nodules, and (iii) a mosaic attenuation pattern (best visible on expiratory images). The present paper summarises the current knowledge, the classification, imaging, and the clinical presentation of bronchiolar disorders.

[Bronchiolar disorders: clinical-radiological assessment and classification]. / Evaluación clínico-radiológica y clasificación de la bronquiolitis del adulto.

Bronchiolar disorders are generally difficult to diagnose. A detailed clinical history may point toward a specific diagnosis. Pertinent clinical questions include history of smoking, collagen vascular disease, inhalation injury, medication use and organ transplantation. It is important also to evaluate possible systemic and pulmonary signs of infection, evidence of air trapping, and high-pitched expiratory wheezing, which may suggest small airways involvement. Pulmonary function tests and plain chest radiography may demonstrate abnormalities; however, they rarely prove sufficiently specific to obviate bronchoscopic or surgical biopsy. High-resolution CT (HRCT) scanning of the chest is often an important diagnostic tool to guide diagnosis in these difficult cases, because different subtypes of bronchiolar disorders may present with characteristic image findings. Some histopathologic patterns of bronchiolar disease may be relatively unique to a specific clinical context but others are nonspecific with respect to either etiology or pathogenesis. Primary bronchiolar disorders include acute bronchiolitis, respiratory bronchiolitis, follicular bronchiolitis, mineral dust airway disease, constrictive bronchiolitis, diffuse panbronchiolitis, and other rare variants. Prominent bronchiolar involvement may be seen in several interstitial lung diseases, including hypersensitivity pneumonitis, collagen vascular disease, respiratory bronchiolitis-associated interstitial lung disease, cryptogenic organizing pneumonia, and pulmonary Langerhans' cell histiocytosis. Large airway diseases that commonly involve bronchioles include bronchiectasis, asthma, and chronic obstructive pulmonary disease. The clinical and prognostic significance of a bronchiolar lesion is best determined by identifying the etiology, underlying histopathologic pattern and assessing the correlative clinic-physiologic-radiologic context.

Small Airway Disease: A Step Closer to Etiology-Based Classification of Bronchiolitis.

Three major histologic patterns of bronchiolitis: obliterative bronchiolitis, follicular bronchiolitis, and diffuse panbronchiolitis, are reviewed in detail. These distinct patterns of primary bronchiolar injury provide a useful starting point for formulating a differential diagnosis and considering possible causes. In support of the aim toward a cause-based classification system of small airway disease, a simple diagnostic algorithm is provided for further subclassification of the above 3 bronchiolitis patterns according to the major associated etiologic subgroups.

Smoking-related interstitial lung disease.

Pulmonary diseases associated with tobacco smoking are a complex group of disorders ranging from chronic obstructive pulmonary disease (COPD) to lung cancer. Interstitial lung diseases (ILDs) have only recently been linked to smoking. The ILDs related to smoking include respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and pulmonary Langerhans cell histiocytosis. The relationship of smoking with each of these entities has been largely established on the weight of epidemiologic evidence. Although they have been retained as distinct and separate conditions in various classifications of interstitial lung diseases, these 3 entities share a number of clinical, radiologic, and pathologic features suggesting that they represent a spectrum of patterns of interstitial lung disease occurring in predisposed individuals who smoke. Evaluation of histologic features, particularly in surgical lung biopsy samples, is important in making the distinction between these disorders. However, even after tissue biopsy, it may sometimes be difficult to clearly separate these entities. The importance of making the distinction between them lies in the different clinical management strategies used. Further experimental evidence, including genetic information, may be important in improving our understanding of these diseases.

[Quality of spirometric measurements in children younger than 10 years of age in the light of the recommendations]. / Jakosc badania spirometrycznego u dzieci 10-letnich i mlodszych w swietle zalecen standaryzacyjnych.

INTRODUCTION: In 2005 the European Respiratory Society/American Thoracic Society (ERS/ATS) published an updated document on the standardization of spirometry (European Respiratory Journal 2005; 26: 319-338). It defines criteria for the acceptability of spirometric measurements. The aim of this retrospective study was to assess the adherence to those standards of flow-volume measurements in children younger than 10 years of age. MATERIAL AND METHODS: The analysis was carried out on the results obtained from 233 children aged 4.2-10 years, referred to a spirometric lab during a period of three months. RESULTS: 116 children (all but one preschool) did not cooperate; the results of the 117 who completed the procedure of flow-volume measurement were analysed using ERS/ATS criteria. 80.3% of the children had back extrapolated volume (Vbe) within the defined limit, but only 23.9% had forced expiratory time > 3 s. FEV(1) and FVC were repeatable in 78.6% of the children. When these three criteria were used together, the measurements were acceptable according to ATS/ERS recommendations in 17.1% of the children. Elimination of the forced expiratory time criterion has further increased their number to 63.2%. CONCLUSIONS: Specific recommendations for children should be developed, as the current requirements appear too restrictive, especially regarding the time of forced expiration.

The interrater reliability of a validated bronchiolitis severity assessment tool.

BACKGROUND: We previously constructed and tested a bronchiolitis severity assessment tool in 2 independent hospitals. The model uses age, work of breathing, dehydration and tachycardia to successfully predict disease severity. OBJECTIVE: To prospectively measure the interrater reliability of a bronchiolitis severity assessment tool and of its component variables. DESIGN: Prospective observational survey. SETTING: A county teaching hospital emergency department serving a mixed urban and rural population with an emergency medicine residency program in 2-3-4 format. SUBJECTS: Thirty-two physicians evaluated a convenience sample of children aged less than 18 months presenting to the emergency department with a clinical diagnosis of bronchiolitis during a single season. METHODS: Two physicians independently examined each patient. Each physician completed a physical examination template that included the variables used in the severity assessment tool. Interrater agreement was measured for the variables work of breathing and dehydration and for the tool as a whole using a weighted kappa statistic. RESULTS: One hundred and forty-six cases were enrolled. Twenty-five were dropped for incomplete data collection. The actual weighted agreement on overall classification was 92%; expected, 73%, kappa = 0.676; P < 0.0001. The actual weighted agreement for dehydration was at 95%; expected, 92%, kappa = 0.305; P = 0.0001. The agreement for work of breathing was 95%; expected, 86%; kappa = 0.611; P < 0.0001. The overall model showed better interrater reliability than its individual components. CONCLUSIONS: Overall interrater reliability for this bronchiolitis severity assessment tool is substantial.

[Non transplant-related constrictive bronchiolitis in adults]. / Bronchiolites constrictives de l'adulte, hors contexte de transplantation.

INTRODUCTION: The term bronchiolitis refers to inflammatory disorders of the bronchioles. Constrictive bronchiolitis is the type most frequently encountered. STATE OF THE ART/PERSPECTIVES: The main clinical manifestations include the development of exertional dyspnoea and fixed airflow obstruction. Chest x-ray findings are usually unhelpful, but CT scanning may reveal a mosaic pattern on expiration. Peripheral micronodules are less frequently seen. The causes of constrictive bronchiolitis are numerous. The diagnosis may be clear from the clinical context when a causative event or predisposing condition can be identified (lung or bone marrow transplantation, toxic fume or gas inhalation, rheumatoid arthritis); in other conditions, a stepwise approach to the diagnosis is usually recommended in order to exclude other causes of subacute or chronic obstructive disease. Formal diagnosis requires histological examination of surgical lung biopsies. Despite corticosteroid administration, respiratory failure usually develops. Specific inhibitors of pro-inflammatory cytokines may offer a new and promising therapeutic approach. CONCLUSIONS: If the clinical context or the radiology and clinical findings are not highly suggestive of a constrictive bronchiolitis, a surgical lung biopsy should be considered.

Adult bronchiolitis--a clinical and pathological interpretative classification.

INTRODUCTION: Bronchiolitis is a heterogeneous group of diseases of an inflammatory nature, centered on small conducting airways and often associated with other pulmonary disorders. No single classification scheme for bronchiolar diseases has been widely accepted. In this retrospective study, it was decided to apply a new clinical and pathological interpretative classification. OBJECTIVES: To propose a new clinical and pathological interpretative classification for adult bronchiolitis, based on statistical analysis of a population of 193 patients with histopathological diagnosis of bronchiolitis. MATERIALS AND METHODS: A retrospective study analyzed the epidemiological characteristics, co-morbidities and radiological findings present in a group of patients with histopathological diagnosis of bronchiolitis. RESULTS: This trial involved 193 cases collected over a period of eleven years; 48 (24.9%) patients had simultaneous pulmonary disease; non-pulmonary diseases, such as cardiovascular diseases, type II Diabetes mellitus and dyslipidemia were present in 57 cases. The image study was extremely important in order to integrate clinical and pathological aspects. In this study respiratory bronchiolitis related to smoking dominated. The radiological findings confirmed the secondary nature of the histopathological features, with prevalence of ground-glass patterns, pneumothorax and patterns of interstitial involvement, as described in the literature. It was also verified that clinical behavior of different forms of bronchiolitis was important to distinguish the various types, since they could progress without typical anatomopathological aspects. CONCLUSION: This trial showed that the vast majority of diagnosis obtained corresponded to bronchiolitis as secondary to pulmonary pathology. In most cases, morphological findings had to be complemented with clinical and radiological characteristics, in order to obtain the final diagnosis.

Follicular bronchitis in the pediatric population.

Five patients in a pediatric population were identified with idiopathic follicular bronchitis (IFB) by open lung biopsy and their case records were reviewed. All were tachypneic and had a chronic cough by 6 weeks of age. The physical examination was characterized by diffuse fine crackles in four patients and by coarse rhonchi in one. The chest radiographs in all demonstrated a diffuse interstitial pattern. None had a collagen vascular or an autoimmune disease demonstrable. Response to corticosteroid therapy was minimal. Associated or coincidental esophageal reflux was treated surgically in two. No viral or bacterial agents were isolated in the sputum or the biopsy specimens. Patients have been followed up for 2 to 15 years; the conditions of all patients improved at about 2 to 4 years of age. The older patients have residual mild obstructive lung disease. To our knowledge, this is the first reported series of IFB in the pediatric population.

Revision of the 1990 working formulation for the classification of pulmonary allograft rejection: Lung Rejection Study Group.

In 1990, an international grading scheme for the grading of pulmonary allograft rejection was instituted. The use of this classification has resulted in a uniformity of grading which has allowed inter-institutional collaborations and communication unique in allograft monitoring. In 1995 an expanded group of international pathologists convened and revised the original proposal. This article summarizes the updated classification for pulmonary allograft rejection. In brief, acute rejection is based on perivascular and interstitial mononuclear infiltrates. Each grade of acute rejection should mention the presence of coexistent airway inflammation, the intensity of which may also be graded. Chronic rejection is divided into bronchiolitis obliterans--active or inactive--and vascular atherosclerosis--accelerated arterial or venous sclerosis.

Bronchiolitis, an update.

Besides the classical forms of acute and chronic bronchiolitis, different special forms, such as obliterative, respiratory, and follicular bronchiolitis are recognized. In addition, even new entities emerge, such as Sauropus-induced bronchiolitis. Despite this progress in pathology, pulmonologists still prefer the diagnostic term 'small airways disease', instead of the more specific and even etiology-directed diagnoses provided by the morphologic examination. In this overview, an updated classification will be presented, which includes all forms of bronchiolitis described so far. This classification is structured along morphologic features of bronchiolitis. Different forms of acute and chronic bronchiolitis are described, so that a given reaction pattern can be associated with specific causes, such as eosinophilic bronchiolitis in asthma, or necrotizing bronchiolitis in viral infection. However, there exist more than just one morphologic reaction for a given etiologic agent, resulting in an overlap of morphologic appearances for a given disease.

The neuroendocrine stress response and severity of acute respiratory syncytial virus bronchiolitis in infancy.

OBJECTIVE: Neuroendocrine hormones have profound effects on the immune system. The immune response is a major factor in the pathogenesis of acute respiratory syncytial virus (RSV) infection. We hypothesised that there is a relationship between the neuroendocrine response in acute RSV infection, the severity of illness, and the degree of lymphopenia. DESIGN: Prospective, non-randomised cohort study of infants hospitalised for RSV infection requiring mechanical ventilation or managed conservatively. The study assessed the effect of age, gender, birth gestation, and severity of illness on stress hormone profile and its relationship to lymphocyte count. SETTING: Regional Paediatric Intensive Care Unit (PICU) and children's wards. PATIENTS: Thirty-two consecutive infants with RSV infection were enrolled, of which thirteen were mechanically ventilated on PICU (study subjects) and nineteen treated on the ward (comparison group). Twenty-three children (72%) returned for follow-up. MEASUREMENTS AND MAIN RESULTS: A specific neuroendocrine profile was found in PICU patients compared to ward patients (Wilks Lambda = 0.36, F = 9.05, P =.03). PICU patients had significantly higher prolactin and growth hormone, and significantly lower leptin and IGF-1. Cortisol levels were the same. PICU patients were more lymphopenic compared to ward patients (P =.0001). On multiple regression analysis, prolactin and leptin levels accounted for 57% of the variation in lymphocyte count. CONCLUSIONS: Whereas the effect of intensive care (mechanical ventilation and medication) could not be controlled for, our results suggest that there is an association between the neuroendocrine hormone response, severity of illness and degree of lymphopenia.

Small airway diseases.

High-resolution CT scan is currently the best imaging technique for assessment of diseases of the bronchioles. This article describes the anatomic basis for the findings. This is followed by a presentation of the findings in bronchiolitis, as it is currently classified, into five main groups: (1) cellular bronchiolitis, (2) panbronchiolitis, (3) respiratory bronchiolitis, (4) constrictive bronchiolitis, and (5) bronchiolitis obliterans with intraluminal polyps.

Overview of bronchiolitis.

Many of the diseases associated with bronchiolitis may produce varying degrees of both histologic manifestations--i.e., proliferative and constrictive bronchiolitis. The factors responsible for producing one pattern or the other are not known. It therefore is important that one consider both the etiologic and histologic classification when attempting to identify a case of bronchiolitis. In some instances, it appears that proliferative bronchiolitis, the more common variety, is an "early" lesion that may completely or partially resolve. Constrictive bronchiolitis is a rare finding and may be the final outcome of persistent and severe proliferative bronchiolitis. Most often, constrictive bronchiolitis appears to be a separate process dependent on the type, extent, and severity of the initial insult.

Bronchiolitis in association with connective tissue disorders.

In general, lung involvement in connective tissue disorders has not been as well defined as has isolated interstitial lung disease; this applies particularly to bronchiolitis, which occurs infrequently. The low prevalence of bronchiolitis may reflect difficulties in making the diagnosis in mild to moderate disease; at present, most reported disease is severe. This is likely to account for the lack of therapeutic success in obliterative bronchiolitis and in many patients with follicular bronchiolitis. There is a need for earlier intervention if treatment is to be effective, and thus there is a need to refine the noninvasive diagnosis of bronchiolitis. This goal is unlikely to be achieved without the systematic noninvasive evaluation and surveillance of large groups of patients with connective tissue diseases. The role of the pulmonary function laboratory in identifying early bronchiolitis remains entirely uncertain; whether silent "small airways disease," defined physiologically, predicts the eventual development of bronchiolitis is unclear. The reversibility of this asymptomatic lesion with inhaled steroid therapy and the role of inhaled treatment in bronchiolitis, in general, have not been evaluated. More work needs to be done to determine the predictive value of CT appearances and BAL findings, to try to identify a subgroup of patients at greater risk of developing severe bronchiolitis. Further histocompatibility studies may serve as a basis for the selection of patients with an increased likelihood of developing airways disease. The role of open lung biopsy requires further clarification. Better noninvasive evaluation should reduce the need for this invasive procedure; in some patients, however, including those with concomitant interstitial lung disease, histologic assessment will remain an essential component of management. In recent years, in contrast to early reports, it has become apparent that organizing pneumonia has a better prognosis than fibrosing alveolitis in the connective tissue diseases; overall, stability or regression of disease, usually with corticosteroid therapy, was documented in 28 of 39 reported cases. In these patients, a tissue diagnosis serves to identify the need for aggressive therapeutic intervention. Finally, the compilation of larger clinical series would improve our understanding of severe bronchiolitis. This is likely to require multicenter collaboration, which often is impracticable; without this approach, however, the description of bronchiolitis will remain anecdotal.