Chest
Volume 139, Issue 2, February 2011, Pages 412-423
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Translating Basic Research into Clinical Practice
Small Airway Disease in Asthma and COPD: Clinical Implications

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Asthma and COPD have a high personal, societal, and economic impact. Both diseases are characterized by airway obstruction and an inflammatory process. The inflammatory process affects the whole respiratory tract, from central to peripheral airways that are <2 mm in internal diameter, the so-called small airways. There is an increased interest in small airway disease, and some new insights have been gained about the contribution of these small airways to the clinical expression of asthma and COPD, as reviewed in this article. Newly developed devices enable drugs to target the small airways, and this may have implications for treatment of patients with asthma, particularly those not responding to large-particle inhaled corticosteroids or those with uncontrollable asthma. The first studies in COPD are promising, and results from new studies are eagerly awaited.

Section snippets

Assessment of Small Airway Disease

The assessment and monitoring of small airway involvement in asthma and COPD is a challenging matter because the region is relatively inaccessible for functional measurements. Until now there has been no test with accepted cutoff values to measure the presence and severity of small airway involvement.

Functional Parameters

Pulmonary small airway function tests have been developed with respect to the physiology of small airways.1 Although the cross-sectional area increases toward the periphery of the lung, gas velocity decreases and airflow changes from turbulent to laminar. Obstruction of the small airways affects the distribution of ventilation and may lead to small airway closure accompanied by air trapping. Pulmonary function tests that are used to assess small airway pathology can be subdivided in tests

Noninvasive Markers of Inflammation

Peripheral airway inflammation can be examined by measuring nitric oxide (NO) concentrations in single breath exhaled air during different flow rates.15 Using a mathematical model, it is possible to discriminate between the bronchial and alveolar contribution. Alveolar NO measurements have shown good reproducibility and responsiveness to small particle inhaled corticosteroids (ICS) (Table 1, Table 2).16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39

Imaging Techniques

Imaging techniques, such as high-resolution CT (HRCT) scanning and MRI with inhaled hyperpolarized gases, can be used to evaluate indirect signs of small airway obstruction, such as inhomogeneity of ventilation and air trapping, which are associated with remodeling.40, 41, 42, 43, 44, 45 All above-mentioned parameters have been used in research and contributed to the progress made to understand involvement of small airways in asthma and COPD. Each test has its own features making it more or

Pathology of Small Airways in Asthma

Despite interest in small airway disease in asthma, the number of articles about the underlying pathology is surprisingly small, probably due to the relative inaccessibility of the small airways. Several studies collected tissue by using lung material from autopsied patients with fatal asthma, or from patients with asthma needing lung resection because of malignancy. More recent studies in subjects with nocturnal asthma used transbronchial biopsies, an invasive technique that limits its use for

Pathology of Small Airways in COPD

COPD is defined as an abnormal inflammatory response of the lung to noxious particles and gases, mainly cigarette smoke.66 The smaller airways (<2 mm in internal diameter) offer little resistance in normal lungs but are the major site of obstruction in COPD. To assess the role of small airways in COPD, we raised the following questions:

Asthma

With the introduction of the solution hydrofluo­roalkane (HFA) technology, pressurized metered dose inhalers (pMDIs) have become available, generating small particles with an average size of approximately 1 μm. Examples of currently available small-particle pMDIs are HFA-beclomethasone, HFA-beclomethasone/formoterol, HFA-flunisolide, and ciclesonide. The most important advantage of small-particle pMDIs is their higher lung deposition than conventional inhalers (50% to 60% vs 10% to 20%) and

Conclusion

There is now a considerable amount of evidence that small-airway inflammation contributes importantly to the clinical expression of asthma and COPD. This is important, since new devices have become available that allow drugs to better target the small airways. Several studies in asthma have shown a larger improvement in small airway function and inflammation with small-particle aerosols than with larger-particle aerosols. This may be clinically relevant, especially for patients with

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