The distal airways: are they important in asthma?

Abstract

Although the airways of <2 mm in diameter have been dubbed the "quiet zone", they do not appear to be so in asthma. Physiological and pathological evidence suggests that the small airways and lung parenchyma participate in asthma pathogenesis, and may explain many of the clinical observations noted.This review presents this evidence, beginning with physiological evidence, followed by pathology and last by imaging studies that evaluate the distal lung. Seminal physiological studies date back to the 1960s, with significant progress in the area of airway smooth muscle and its contribution to airways responsiveness noted over the last several years.The use of bronchoscopy in clinical studies has complemented the autopsy studies in advancing knowledge about airway structural changes appreciated in asthma in the small airways and lung parenchyma. These pathological studies have allowed validation of the physiological, and more recently the imaging studies performed to evaluate this compartment of the lung in asthma.Thus, the evidence suggests that the small airways and parenchyma contribute significantly to asthma pathogenesis. The challenge now lies in evaluating this compartment in the context of its value as a therapeutic target in asthma. Eur Respir J 1999; 14: 1403±1417. Data from the last three decades have suggested that the distal lung, which includes the airways of <2 mm and the lung parenchyma, contributes to asthma pathogenesis. Due to the challenges raised in evaluating this part of the lung, this region has not been studied in the same level of detail as have the larger airways. However, a significant amount of pathological data from autopsy specimens and recently from chronic, stable asthmatics, evaluating the small airways and lung parenchyma, are available. These data, combined with physiological data, support a significant role for the distal lung as a contributor to airway inflammation and hyperresponsiveness. The following review will present this evidence and explore the clinically important issue of the distal lung as a therapeutic target in asthma. Physiology of the distal airways Animal and in vitro studiesThe small airways of <2 mm in diameter are pathways of low resistance, and normally contribute~10% of the total resistance to flow. These observations were made in, seminal contributions by MACKLEM and MEAD [1, 2] using a retrograde catheter technique. Using excised dog lobes, they placed a catheter containing bell shaped polyethylene tubing at one end. The bell was wedged into a bronchus with the catheter extending peripherally through the parenchyma and pleura. They showed that the peripheral resistance (Rp) was too small to detect at >80% of vital capacity (VC), but increased at lower volumes to 15% of the total lung resistance at 1% of VC. These data are in keeping with WEIBEL [3], who demonstrated that the cross-sectional area of the small airways was significantly larger than that of the central airways. BROWN et al. [4] further evaluated the effects of small airways occlusion...

Is it really time to look at distal airways to improve asthma phenotyping and treatment?

“…Distal airway inflammation has been demonstrated by a number of histopathological studies using lung resection specimens or transbronchial biopsies [2]. Taken together, these data suggest an important role for distal airway inflammation in severe asthma.…”

n-3 Fatty acids and asthma

“…These episodes are generally associated with airflow obstruction (bronchoconstriction) within the lungs that is often reversible either spontaneously or with treatment. In most asthmatics, inflammation is largely restricted to the conducting airways but with an increase in disease severity, the inflammatory infiltrate spreads to the small airways and in some cases adjacent alveoli (13) . Another feature of asthma is the response to triggers such as exercise and allergic sensitisation; the airways recognise common triggers and in turn generate a Th2-type cytokine response to them.…”

The early allergic response in small airways of human precision-cut lung slices

“…Small airways have been defined as those with a diameter of v2 mm [1,2]. As a result of their relative inaccessibility, their role in human asthma has only been poorly defined.…”

“…The role of small airways (v2 mm in diameter) in the disease process of bronchial asthma is still unresolved, but awareness of their importance is growing [1][2][3]. On the basis of measurements with the retrograde catheter technique in animals, MACKLEM and MEAD [4] determined that the small airways contribute v10% of the total airway resistance and hence termed them the "quiet zone".…”