Respiratory diseases frequently involve the small airways, yet many respiratory therapists lack a real understanding of the concept of small airways disease - and with good reason. The definition of "small airways disease" varies based on one's perspective.
A pulmonologist may consider small airways disease as a group of lung disorders involving the terminal airways assessed by airflow obstruction, while a radiologist might define it by evaluating high-resolution computed tomography scan changes. A pathologist would likely identify small airways disease based on histological specimens.
A number of diseases fall under the general umbrella of small airways disease. Small airways usually are defined as airways <2 mm in internal diameter absent of cartilage.
Because classifications of lung diseases change and overlap, classification of small airways disease has varied. One method to classify small airways diseases is to determine whether the disease is primary to the small airways or secondary to other lung disease, such as asthma or smoke exposure.
Research shows that in healthy subjects, small conducting airways are thin-walled and offer little resistance to airflow that is laminar. Resistance to airflow varies inversely to the fourth power of the airway radius. Therefore a 50 percent decrease in airway radius results in a 16-fold increase in resistance to airflow. This decrease in airway radius may result from increased amounts of mucus and inflammatory cells obstructing the airway lumen, increased thickness of the submucosa, fibrosis, or increased smooth muscle mass or contraction.
Bronchiolitis is a generic term clinically used to describe a variety of inflammatory conditions involving the small airways. The inflammatory conditions may be acute, chronic, or both acute and chronic:
Acute bronchiolitis is common among infants and young children and is recognized as the most common respiratory diagnosis during the first year of life.1 Its etiology is variable but generally infectious, and approximately 75 percent of cases are due to respiratory syncytial virus (RSV). Infants typically present with wheezing, tachypnea, and tachycardia. More severe cases will result in chest retraction, nasal flaring, and lung hyperinflation. A high-resolution chest CT may show branching linear opacities.
Chronic bronchiolitis describes a pattern in which bronchioles contain chronic inflammatory cells. Chronic bronchiolitis may be a feature of various diseases, and symptoms may overlap with acute bronchiolitis. Fibrosis may or may not be present in association with chronic bronchiolitis. However, the presence of lung fibrosis indicates some level of irreversibility in the disease process.
Tobacco-associated bronchiolitic disease (membranous bronchiolitis and respiratory bronchiolitis) are terms used to label the extensive and variably severe inflammatory and fibrotic changes caused by tobacco smoke. These changes are found in both the terminal and respiratory bronchioles. Patients are often asymptomatic, but pulmonary function evaluation may show obstructive change such as decreased expiratory flow rates. Other smoking-related lung changes include chronic bronchitis and emphysema.
Small airways in asthma, COPD
Airway inflammation and remodeling occur in both the large and small airways. Although small airways add little to airway resistance in healthy patients, they are the major site of airflow limitation in both asthma and COPD.
Additionally, distal lung inflammation is present in even those with mild asthma without persistent symptoms. The predominance of distal or small airway obstruction in asthma has resulted in the understanding that it is a disease of the entire respiratory tract. Reasonably then, RTs should consider the small airways as a target for medication delivery.
It is now accepted that in asthma, inflammatory cells, in particular eosinophils and T cells, increase in the small airways and the lung parenchyma. This finding may prove to be important because the total volume and combined surface area of the small airways are much greater than the combined volume and the surface area of the large airways. Peripheral airways also have been recognized as a predominant site of airflow obstruction in asthmatics.2
COPD is defined as an abnormal inflammatory response of the lung to noxious particles and gases, mainly cigarette smoke.3 Airways <2 mm in diameter, which represent <10 percent of total airway resistance in healthy subjects, contribute to the majority of the abnormally high resistance work in patients with COPD. This increased resistance may be related to a reduction in small airway numbers and/or narrowing of small airways.
Evaluation of small airways function
Features of the various small airways diseases overlap, and a firm diagnosis may not be possible with limited bronchoscopy-derived information. Pulmonary function, imaging and clinical relationships may be necessary for accurate assessment.
Characteristics of small airways obstruction include premature airway closure and air trapping. Residual volume (RV) is elevated in the presence of premature airway closure and air trapping. Total lung capacity (TLC) is commonly increased in obstructive disease.
The RV/TLC ratio is considered a valuable indice of elevation of RV and is also considered the first step of hyperinflation. The forced expiratory flow at 25 to 75 percent of force vital capacity (FEF25-75%) is the spirometric variable cited as an indicator of small airways obstruction. By excluding the initial peak of expiratory flow and averaging flow rate over the mid-quartile range of FVC, the FEF25-75% is sensitive to the same small airways characteristics and flow limitation.
Imaging with CT also allows assessment of small airways in obstructive pulmonary diseases. High-resolution CT allows direct assessment of large and medium airways (diameter >2-2.5 mm), and indirect assessment of small airways.
Areas of mosaic lung attenuation on inspiratory CT and air trapping on expiratory CT have been evaluated as markers of small airways disease in both asthma and COPD. Yet there is a concern that this use of CT using ionizing radiation may increase risk of malignancy, especially in younger females.
Several investigators have explored the relationship between small airways in asthmatics and alveolar nitric oxide (NO), proposed as a marker of small airways involvement in asthma. One study measured exhaled NO and small airways function using single breath nitrogen washout in 16 subjects with mild asthma. The author found that exhaled NO was positively associated with the phase III slope (dN2) of single breath washout curve, indicating an association between exhaled NO and small airways function.4 However, exhaled NO is not selective for small versus large airways.
Therapeutic treatment options
Accumulating evidence suggests that airway inflammation occurs throughout the entire airway. Therefore, it is possible that poorly controlled inflammation in the distal airways may contribute to accelerated decline in lung function because conventional inhaled steroids do not penetrate to the distal lung. Clearly, there is a need to assess distal lung and parenchymal inflammation in all degrees of asthma.
Early diagnosis of small airway dysfunction is important because treatment during the early stages of the disease may aid in the prevention of irreversible airway damage. Studies have shown that the central airways are the primary target for most of today's inhaled corticosteroids. Small airways typically receive less than 30 percent of the inhaled dose from the majority of available MDI and DPI preparations.2 Yet evidence suggests that the hydrofluoralkane propellants (HFA) promote improved small airway drug deposition compared to the traditional chlorofluorocarbon (CFC) formulations. HFA formulations result in extra-fine drug particles, which are deposited in the large as well as in the small airways of the lung.
Can targeting all airways (both large and small) lead to clinical improvement? Clinical studies were performed with extrafine formulation of ICS delivered via HFA. In patients with asthma, the dose of conventional non-extrafine BDP (delivered via CFC) required to achieve an improvement in pulmonary function is 2.5 times greater than the dose of HFA-extrafine formulation required to produce the same increase in FEV1.5 Another study examined the effects of switching to HFA-BDP in 40 patients with asthma and COPD treated with conventional inhaled steroids. After eight weeks, HFA-BDP demonstrated a greater improvement in spirometric values, respiratory symptoms and beta2-agonist use.6
Many questions remain regarding the role of small airways in lung disease. How does the disease progress? At what stage can interventions slow disease progression or reverse lung damage? Should spirometry be routinely performed? Are routine imaging assessments worthwhile? Can we target inhaled medication therapy more effectively in terms of site-specific drug delivery?
However, there is considerable evidence that small airway inflammation contributes to the clinical expression of asthma and COPD. Newly developed devices enable drugs to target the small airways, and this may be clinically relevant in the treatment of patients with asthma and other pulmonary disease. Drug delivery that favors the small airways may improve some disease management and outcomes.
Alphonso Quinones, DHAC, MA, RT, RRT-NPS, RPFT, RPSGT, AE-C, FACHE, is director of respiratory therapy at North Shore University Hospital, president of Quinones Healthcare Seminars, and chairman of New York State Respiratory Licensure Board. He is also an assistant professor at Molloy College.