Pathophysiology of the Small Airways

 

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ABSTRACT

This review describes, in some detail, the normal structure of the small airways, how this structure is achieved during the development of the bronchial tree from embryogenesis to adulthood, and how the structure determines the function of the airways at different ages and in disease. We then describe the structural abnormalities in small airways in chronic obstructive pulmonary disease (COPD) and their relationship with the disordered pulmonary function found in this disease, as an example of the mechanisms leading to airflow limitation in diseased airways. We address the pathology of small airways in different stages of COPD, summarizing the structural abnormalities associated with the progressive deterioration of pulmonary function from smokers with normal lung function to smokers with severe COPD. The importance of the elastic recoil in the normal and abnormal function of the airways is also highlighted.

REFERENCES

• 1 Mead J. The lung's “quiet zone”.  N Engl J Med . 1970;  282 1318-1319
  PubMedGoogle Scholar
• 1a Burri P H. Development and growth of the human lung. In: Fishman AP, Fisher AB, eds. Handbook of Physiology: The Respiratory System, section 3: Respiration Bethesda, MD: American Physiological Society; 1985
  Google Scholar
• 2 Burri P H. Postnatal development and growth. In: Crystal RG, West JB, eds. The Lung: Scientific Foundations, section 4 New York: Raven Press; 1991
  Google Scholar
• 3 Thurlbeck W M. Pre- and postnatal organ development. In: Chernick V, Mellins RN, eds. Basic Mechanisms of Pediatric Respiratory Disease: Cellular and Integrative Philadelphia: Decker 1991: 23-25
  Google Scholar
• 4 Reid L. The embryology of the lung. In: de Renck AVS, Porter S, eds. Ciba Foundation: Symposium on Development of the Lung London: Churchill; 1967
  Google Scholar
• 5 Plopper C G, Thurlbeck W M. Growth, ageing and adaptation. In: Murray JF, Nadel JA, eds. Textbook of Respiratory Medicine Philadelphia: WB Saunders 1994: 36-49
  Google Scholar
• 6 Hogg J, Williams J, Richardson J, Macklem P, Thurlbeck W. Age as a factor in the distribution of lower-airway conductance in the pathologic anatomy of obstructive lung disease.  N Engl J Med . 1970;  282 1283-1287
  PubMedGoogle Scholar
• 7 Bryan A C, Mansell A L, Levison H. Development of the mechanical properties of the respiratory system. In: Hosdon WA, ed. Development of the Lung New York: Marcel Dekker; 1977;445-468. Lung Biology in Health and Disease Series
  Google Scholar
• 8 Staub N C, Albertine K H. Anatomy of the lung. In: Murray JF, Nadel JA, eds. Textbook of Respiratory Medicine Philadelphia: WB Saunders 1994: 3-35.
  Google Scholar
• 9 Meyrick B, Reid L M. Ultrastructure of alveolar lining and its development. In: Hosdon WA, eds. Development of the Lung New York: Marcel Dekker 1977;135-214. Lung Biology in Health and Disease Series
  Google Scholar
• 10 Boyden E A. Notes on the development of the lung in infancy and early childhood.  Am J Anat . 1967;  121 249-262
  CrossrefPubMedGoogle Scholar
• 11 Boyden E A. Development of the human lung. In: Kelley VC, ed. Brennerman's Practice of Pediatrics Vol 4. Hagerstown: Harper and Row 1972
  Google Scholar
• 12 Landau L D, Lifshitz E M. Viscous fluids. In: Fluid Mechanics 2nd ed. New York: Pergamon 1987: 44-94
  Google Scholar
• 13 Hogg J C, Macklem P T, Thurlbeck W M. Site and nature of airway obstruction in chronic obstructive lung disease.  N Engl J Med . 1968;  278 1355-1360
  CrossrefPubMedGoogle Scholar
• 14 Niewoehner D E, Klienerman J, Rice D. Pathological changes in the peripheral airways of young cigarette smokers.  N Engl J Med . 1974;  291 755-758
  CrossrefPubMedGoogle Scholar
• 15 Cosio M G, Ghezzo H, Hogg J C. et al . The relationships between structural changes in small airways and pulmonary-function tests.  N Engl J Med . 1978;  298 1277-1281
  PubMedGoogle Scholar
• 16 Cosio M G, Majo J, Cosio M G. Inflammation of the airways and lung parenchyma in COPD: role of T cells.  Chest . 2002;  121 (suppl 5) S160-S165
  CrossrefPubMedGoogle Scholar
• 17 Pauwels R A, Buist A S, Calverley P M, Jenkins C R, Hurd S S. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary.  Am J Respir Crit Care Med . 2001;  163 1256-1276
  CrossrefPubMedGoogle Scholar
• 18 Petty T L, Silvers G W, Stanford R E, Baird M D, Mitchell R S. Small airway pathology is related to increased closing capacity and abnormal slope of phase III in excised human lungs.  Am Rev Respir Dis . 1980;  121 449-456
  PubMedGoogle Scholar
• 19 Vanhoutte P M. Airway epithelium and bronchial reactivity.  Can J Physiol Pharmacol . 1987;  65 448-450
  PubMedGoogle Scholar
• 20 Berend N. Lobar distribution of bronchiolar inflammation in emphysema.  Am Rev Respir Dis . 1981;  124 218-220
  PubMedGoogle Scholar
• 21 Hulbert W M, McLean T, Hogg J C. The effect of acute airway inflammation on bronchial reactivity in guinea pigs.  Am Rev Respir Dis . 1985;  132 7-11
  PubMedGoogle Scholar
• 22 Bosken C H, Hards J, Gatter K, Hogg J C. Characterization of the inflammatory reaction in the peripheral airways of cigarette smokers using immunocytochemistry.  Am Rev Respir Dis . 1992;  145 911-917
  PubMedGoogle Scholar
• 23 Finkelstein R, Fraser R S, Ghezzo H, Cosio M G. Alveolar inflammation and its relation to emphysema in smokers.  Am J Respir Crit Care Med . 1995;  152 1666-1672
  CrossrefPubMedGoogle Scholar
• 24 Saetta M, Di Stefano A, Turato G. et al . CD8+ T lymphocytes in the peripheral airways of smokers with chronic obstructive pulmonary disease.  Am J Respir Crit Care Med . 1998;  157 822-826
  PubMedGoogle Scholar
• 25 O'Shaughnessy T C, Ansari T W, Barnes N C, Jeffery P K. Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8+ T lymphocytes with FEV₁ .  Am J Respir Crit Care Med . 1997;  155 852-857
  PubMedGoogle Scholar
• 26 Majo J, Ghezzo H, Cosio M G. Lymphocyte population and apoptosis in the lungs of smokers and their relationship with emphysema.  Eur Respir J . 2001;  17 946-953
  CrossrefPubMedGoogle Scholar
• 27 Macklem P T. The physiology of small airways.  Am J Respir Crit Care Med . 1998;  157(suppl 5, pt 2) S181-S183
  PubMedGoogle Scholar
• 28 Saetta M, Turato G, Baraldo S. et al . Goblet cell hyperplasia and epithelial inflammation in peripheral airways of smokers with both symptoms of chronic bronchitis and chronic airflow limitation.  Am J Respir Crit Care Med . 2000;  161 1016-1021
  CrossrefPubMedGoogle Scholar
• 29 Tashkin D P, Altose M D, Connett J E, Kanner R E, Lee W W, Wise R A. Methacholine reactivity predicts changes in lung function over time in smokers with early chronic obstructive pulmonary disease. The Lung Health Study Research Group.  Am J Respir Crit Care Med . 1996;  153 1802-1811
  PubMedGoogle Scholar
• 30 Lambert R K, Wiggs B R, Kuwano K, Hogg J C, Parè P D. Functional significance of increased airway smooth muscle in asthma and COPD.  J Appl Physiol . 1993;  74 2771-2781
  PubMedGoogle Scholar
• 31 Wright J L, Hobson J, Wiggs B R, Pare P D, Hogg J C. Effect of cigarette smoking on structure of the small airways.  Lung . 1987;  165 91-100
  CrossrefPubMedGoogle Scholar
• 32 Cosio M G, Hale K A, Niewoehner D E. Morphologic and morphometric effects of prolonged cigarette smoking on the small airways.  Am Rev Respir Dis . 1980;  122 265-271
  PubMedGoogle Scholar
• 33 Petty T L, Silvers G W, Stanford R E, Baird M D, Mitchell R S. Small airway pathology is related to increased closing capacity and abnormal slope of phase III in excised human lungs.  Am Rev Respir Dis . 1980;  121 449-456
  PubMedGoogle Scholar
• 34 Bignon J, Khoury F, Even P, Andre J, Brouet G. Morphometric study in chronic obstructive bronchopulmonary disease. Pathologic, clinical, and physiologic correlations.  Am Rev Respir Dis . 1969;  99 669-695
  PubMedGoogle Scholar
• 35 Matsuba K, Thurlbeck W M. The number and dimensions of small airways in emphysematous lungs.  Am J Pathol . 1972;  67 265-276
  PubMedGoogle Scholar
• 36 Saetta M, Ghezzo H, Kim W D. et al . Loss of alveolar attachments in smokers: an early morphometric correlate of lung function impairment.  Am Rev Respir Dis . 1985;  132 894-900
  PubMedGoogle Scholar
• 37 Turato G, Zuin R, Miniati M. et al . Airway inflammation in severe chronic obstructive pulmonary disease: relationship with lung function and radiologic emphysema.  Am J Respir Crit Care Med . 2002;  166 105-110
  CrossrefPubMedGoogle Scholar
• 38 Hale K A, Ewing S L, Gosnell B A, Niewoehner D B. Lung disease in long-term cigarette smokers with and without chronic air-flow obstruction.  Am Rev Respir Dis . 1984;  130 716-721
  PubMedGoogle Scholar
• 39 Nagai A, West W W, Paul J L, Thurlbeck W M. The National Institutes of Health Intermittent Positive Pressure Breathing trial: pathology studies, I: Interrelationship between morphologic lesions.  Am Rev Respir Dis . 1985;  132 937-945
  PubMedGoogle Scholar