Distal lung inflammation in asthma

doi:10.1016/S1081-1206(10)61926-6

Annals of Allergy, Asthma & Immunology

Volume 89, Issue 2, August 2002, Pages 119-124

https://doi.org/10.1016/S1081-1206(10)61926-6 Get rights and content

Objective

To review the role of distal lung inflammation in asthma.

Data Sources and Study Selection

Selected peer-reviewed research publications retrieved from MEDLINE search. Search was restricted to English-language publications only. Included articles were selected for their relevance to pathophysiology, diagnosis, and treatment. Bibliographies of selected papers served as an additional source of considered publications.

Results

Inflammation in the small airways and alveolar tissue plays an important role in the clinical manifestations of asthma. Diagnostic modalities such as transbronchial biopsy and evolving radiologic techniques such as high-resolution computed tomography are improving our ability to evaluate this portion of the lung. New ultra-fine particle size metered-dose inhalers and oral agents such as cysteinyl leukotriene receptor antagonists offer new opportunities for treating small airways inflammation and need to be fully evaluated for their ability to target and treat distal lung inflammation.

Conclusions

Distal lung inflammation is an important component of airway inflammation in asthma. New modalities for evaluating distal airway inflammation and for targeting the distal lung with inhaled and systemic drugs are rapidly expanding our knowledge of the clinical importance of distal lung inflammation and may ultimately be of critical importance in asthma therapy.

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Cited by (22)

Role of Small Airways in Asthma
2016, Immunology and Allergy Clinics of North America
Citation Excerpt :
This study suggests that FEF 25% to 75% and M:P ratio may not be reflective of distal airway inflammation and may not be the best reliable measurements of the inflammation in distal airways. Thoracic gas volume and total lung capacity may be better measurements of distal airway inflammation, as they correlate with distal airway eosinophil count.27 Impulse oscillometry (IOS) is another noninvasive objective measurement of lung function and particular values are associated with the small airways.
Role of FEF<inf>25%-75%</inf> as a predictor of bronchial hyperreactivity in allergic patients
2006, Annals of Allergy, Asthma and Immunology
The small airways may play an important role in the clinical manifestations of asthma. Forced expiratory flow between 25% and 75% (FEF_25%–75%) has been proposed as an approximate measure of the caliber of distal airways. Bronchial hyperreactivity (BHR) is a feature of asthma.
To evaluate the possible role of FEF_25%–75% as a predictor of BHR in allergic patients with asthma and rhinitis.
A total of 726 patients (mean ± SD age, 24.7 ± 6.3 years) were evaluated. Spirometry and methacholine bronchial challenge were evaluated in all the participants.
A difference between forced expiratory volume in 1 second and FEF_25%–75% greater than 20 or a ratio between these variables greater than 1.24 discriminates between patients with no response to a mild response to methacholine vs patients with a moderate-to-severe response with high sensitivity (P < .001).
This study highlights the possible role of FEF_25%–75% in predicting BHR in allergic individuals with airway disorders.
Comparative improvement of asthma symptoms and expiratory flows after corticosteroid treatment: A method to assess the effect of corticosteroids on large vs. small airways?
2006, Respiratory Medicine
The magnitude of improvement of respiratory symptoms (RS) and expiratory flows (EF) following corticosteroid treatment may vary from one asthmatic patient to another. The distribution of ratio of improvement of the above parameters was assessed in 937 patients with asthma of variable severity who took part in three clinical trials comparing the effects of chlorofluorocarbon-propelled beclomethasone dipropionate (CFC-BDP) with similar (n:316) or half-doses (n:581) of extrafine hydrofluoroalkane-propelled (HFA-BDP) on asthma control. We calculated the ratio of improvement of shortness of breath, wheezing, sleep disturbance, cough, and chest tightness over the following physiological parameters: forced expiratory volume in 1 s (FEV₁), FEF_25/75%, morning peak expiratory flow, and FVC, from the baseline value to the last set of measures in the study, while on the study medication. We hypothesized that the ratio of RS/EF would have a normal distribution and would be higher with extrafine HFA-BDP compared with CFC-BDP, which has a larger particle size, when FEV₁ is used, as it mostly assesses large airways. Ratios of improvement were normally distributed for both drugs and no significant shift in its distribution curve was found for HFA-BDP. The ratio of changes in FEF_25/75%/FEV₁ was similar in the two groups. In conclusion, the ratio of improvement of RS/EF is normally distributed over a narrow range, showing a generally good correlation between improvements in EF and symptoms in asthma; it was, however, similar for the two BDP molecules tested. This may suggest that this ratio is not useful for evaluating the effect of corticosteroids on small airways, or that extrafine HFA-BDP acts at the level of large- to moderate-caliber airways to produce most of its beneficial effect.
The role of the small airways in childhood
2004, Revue des Maladies Respiratoires
L’asthme, affection chronique la plus fréquente en pédiatrie, se caractérise par un processus inflammatoire impliquant les voies aériennes proximales et distales, avec des phénomènes de remodelage des voies aériennes et d’altérations de la fonction respiratoire.
Les travaux récemment réalisés chez l’enfant mettent en évidence une atteinte des petites voies aériennes identique à celle de l’adulte. En effet, la présence de cellules inflammatoires ainsi que des altérations structurales des voies aériennes distales ont été retrouvées soit sur des biopsies bronchiques de l’enfant soit sur des produits de lavage bronchoalvéolaire de nourrissons et jeunes enfants. Sur le plan fonctionnel, cette atteinte est objectivée par une diminution du débit expiratoire maximal médian entre 25 et 75 % de la capacité vitale. Celle-ci s’exprime également par l’existence de bronches à parois épaisses ou de plages hypodenses à la tomodensitométrie thoracique en haute résolution. Il semble que les traitements inhalés conventionnels restent sans effet sur les petites voies aériennes. Enfin, les principaux facteurs pronostiques de cette atteinte distale sont représentés par les infections respiratoires et l’exposition tabagique in-utero.
L’atteinte des petites voies aériennes dans l’asthme de l’enfant plaide en faveur de la nécessité de nouvelles thérapeutiques ciblées sur cette partie de l’appareil respiratoire.
L’inflammation et le remodelage des petites voies aériennes sont précoces et durables chez l’enfant asthmatique dont l’appareil respiratoire est en pleine croissance.
Asthma, the most common chronic disease in paediatrics, is characterised by an inflammatory process involving the proximal and distal airways, with remodelling of the airways and changes in respiratory function.
Recent studies in children have provided evidence of damage to the small airways identical to that occurring in adults. In fact inflammatory cells as well as structural alterations of the airways have been found in both bronchial biopsies and broncho-alveolar lavage fluid in infants and young children. At the functional level this damage is manifest by a reduction in maximum expiratory flow rates between 25-75% of the vital capacity. It also shows itself by the demonstration of thick walled bronchi and hypodense bands on the high resolution CT scan. It appears that conventional inhaled treatments have no effect on the small airways. Finally the main prognostic factors for this distal damage are respiratory infections and exposure to tobacco in utero.
Damage to the small airways in childhood asthma indicates the need for new therapies aimed at this part of the respiratory system.
Inflammation and remodelling of the small airways develops early in an asthmatic child whose respiratory system is growing rapidly and persists throughout life.
Physician attitudes, opinions, and referral patterns: Comparisons of those who have and have not taken an allergy/immunology rotation
2004, Annals of Allergy, Asthma and Immunology
Interest in the field of allergy/immunology (A/I) is increasing, yet resident training programs are under pressure to shorten elective rotations such as A/I. It is unclear if there are differences between those who have and have not taken an A/I rotation.
To evaluate differences in the attitudes, opinions, and referral patterns between physicians who have and have not taken an A/I rotation.
An anonymous questionnaire was sent to 375 primary care physicians at one academic medical center. Subjects were separated into 5 cohorts based on specialty and level of training (internal medicine faculty, internal medicine resident, pediatric faculty, pediatric resident, and internal medicine–pediatric resident).
Of the participants, 227 (61.0%) completed the survey. Compared with those who had not taken an A/I rotation, those who had taken an A/I rotation were more likely to feel they knew the types of cases seen by an allergist (75.9% vs 33.3%), to feel they knew an adequate amount about A/I (59.3% vs 19.5%), to feel they were exposed to an adequate amount of A/I during residency (64.8% vs 9.8%), to view immunotherapy as effective (70.0% vs 52.3%), and to have referred a patient to an allergist (77.8% vs 46.0%).
There are significant differences in the attitudes, opinions, and referral patterns between physicians who have and have not taken an A/I rotation. Allergic diseases are increasing, yet residency training programs are under pressure to shorten rotations such as A/I to accommodate federally mandated work hour restrictions. The potential for inadequate care of allergic diseases may be an important issue if these trends continue.
Physiologic correlates of distal lung inflammation in asthma
2004, Journal of Allergy and Clinical Immunology
The distal lung is an important site of inflammation in asthma. Maximal midexpiratory flows and the ratio of maximal:partial flows are purported to reflect distal lung function.
We obtained contemporaneous transbronchial biopsy, spirometry, and plethysmography to describe more accurately the relationship between physiology and distal lung inflammation in asthma.
Ten patients with severe, persistent asthma with mean ± SE FEV₁ of 2.8 ± 0.2 L and overnight fall in FEV₁ of 22.8% ± 3.8% underwent transbronchial biopsy, spirometry, maximal midexpiratory flows, maximal:partial ratio, and lung volumes, all at 4 am. Morphometric analysis was performed after immunohistochemistry for eosinophils, lymphocytes, macrophages, mast cells, and neutrophils.
Maximal midexpiratory flows, maximal:partial ratio, FEV₁, and forced vital capacity were not significantly correlated with alveolar tissue inflammation. However, the degree of eosinophilic alveolar inflammation was significantly and positively correlated with both total lung capacity (Spearman ρ = 0.70; P = .03) and thoracic gas volume (ρ = 0.62; P = .05). Correlation between eosinophils and other lung volumes was not observed. Other inflammatory cell types did not correlate with lung volumes.
Purported physiologic measures of distal lung function are poorly correlated with histopathologic evidence of distal lung inflammation. Measurement of lung volumes more accurately reflects eosinophilic distal lung inflammation.

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: Supported by a grant from AstraZeneca LP

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REVIEW ARTICLEDistal lung inflammation in asthma

Objective

Data Sources and Study Selection

Results

Conclusions

Chest

Chest

J Lipid Mediat Cell Signal

J Biol Chem

Peripheral lung resistance in normal and asthmatic subjects

Am Rev Respir Dis

Airway-parenchyma uncoupling in nocturnal asthma

Am J Respir Crit Care Med

The structure of large and small airways in nonfatal and fatal asthma

Am Rev Respir Dis

Inflammatory cell distribution within and along asthmatic airways

Am J Respir Crit Care Med

Alveolar tissue inflammation in asthma

Am J Respir Crit Care Med

Mucosal inflammation in asthma

Am Rev Respir Dis

Lymphocyte and eosinophil influx into alveolar tissue in nocturnal asthma

Am J Respir Crit Care Med

Evaluation of airways in obstructive pulmonary disease using high-resolution computed tomography

Am J Respir Crit Care Med

Human airway narrowing measured using high resolution computed tomography

Am J Respir Crit Care Med

REVIEW ARTICLE
Distal lung inflammation in asthma