Is Asthma Really a Risk Factor for COPD?Jennifer Ann Mendoza-Wi, MD, FCCPPhilippine College of Chest PhysiciansRESPINA 2004

Asthma and COPD-DefinitionsAsthma: BHR, airway inflammation, airflow obstruction, which may be relieved spontaneously or with medication.Most frequently diagnosed during childhoodAssociated with atopy and eosinophilic inflammationCOPD: a chronic and usually progressive disease characterized by airflow limitation that is not fully reversibleMost frequently diagnosed during the middle or late lifeAssociated with neutrophilic inflammation

Similarities and Differences in Asthma & COPD: The Dutch HypothesisIn 1995, the ATS stated it may be impossible to differentiate patients with asthma whose airflow obstruction does not remit completely from persons with chronic bronchitis and emphysema with partially reversible airflow obstruction and bronchial hyperresponsiveness (BHR).

Similarities and Differences in Asthma & COPD: The Dutch HypothesisNumerous studies have documented the presence of partial reversibility after short-term and long-term bronchodilator administration in patients with COPD. This partial reversibility contrasts with asthma which has variable and reversible airflow obstruction

Similarities and Differences in Asthma & COPD: The Dutch Hypothesisthere is increasing scientific and clinical evidence that asthma and COPD share many common origins (ie, epidemiologic characteristics and clinical manifestations)

Orie and coworkers, 1961Bleecker ER, CHEST 2004; 126 (2), 93S-95SPostma DS et al, CHEST 2004; 126 (2) 96S-104S

Bleecker, E. R. Chest 2004;126:93S-95SCharacteristics of asthma and COPD

Similarities and Differences in Asthma & COPD: The Dutch HypothesisCOPD and asthma are not distinct entities in selected individuals, and that similar pathogenetic mechanisms may be involved in the pathogenesis of asthma and COPD in some individuals. Orie and coworkers, 1961Bleecker ER, CHEST 2004; 126 (2), 93S-95SPostma DS et al, CHEST 2004; 126 (2) 96S-104S

Similarities and Differences in Asthma & COPD: The Dutch HypothesisThe three components of the hypothesis:Overlapping clinical features (symptoms, allergy, BHR) of OLD may define the specific clinical phenotype One form of OLD (asthma) may evolve into another (COPD)OLD is based on allergy (ie. inflammation) and BHR, and endogenous (host) factors determined by heredity (genes), but is modulated by exogenous (ie environmental) factors (eg. allergens, infections, smoking, pollution, age, and airway geometry)

Bleecker, E. R. Chest 2004;126:93S-95SPotential interactions between asthma and COPD

Similarities and Differences in Asthma & COPD: The British Hypothesisproposes that asthma and COPD are distinct clinical entities that are generated by distinct mechanisms.

Elias,J: CHEST 2002; 126(2), 111S-115S

The Relationship Between Asthma & COPDTissue injury- proteolysis/apoptosis/remodelingCOPD/EmphysemaAsthmaProposed relationship between asthma and emphysemaElias,J: CHEST 2002; 126(2), 111S-115S

The Relationship Between Asthma and COPDStructural alterations are prominent in asthmatic airways (airway remodelling)Mucous responses in patients with chronic bronchitis and asthma are similar

The Relationship Between Asthma & COPDElias,J: CHEST 2002; 126(2), 111S-115S

Physiologic Similarities and Differences Between COPD and AsthmaSignificant overlap exists in individual patients with respect to airway wall thickening and low-attenuation parenchymal regions on CT scan,Reversibility and airway hyperresponsivenesslung diffusion resting and dynamic hyperinflationlung elastic recoil exercise response pharmaceutical volume reduction effect following therapy with bronchodilatorsSciurba FC, CHEST 2004;126: 117S-123S

Sciurba, F. C. Chest 2004;126:117S-124SCT scans of two subjects with clinical histories that are consistent with COPD are shown

The Physiologic Dogma: Asthma vs COPDThe most common working definitions of COPD and asthma in most clinical and research settings consistently incorporate the following physiologic attributes:Degree of Variability and Reversibility of SpirometryDiffusing capacityHyperinflationLung elastic recoil/lung complianceSciurba FC, CHEST 2004;126: 117S-123S

The Physiologic Dogma: Asthma vs COPDMore physiologic attributes:Simple measures of Pulmonary function in asthma and COPD ( rate of decline in lung function which in a significant group of asthma patients evolves into incompletely reversible disease)Bronchodilator reversibility and AHRResting and dynamic hyperinflationSciurba FC, CHEST 2004;126: 117S-123S

Sciurba, F. C. Chest 2004;126:117S-124STwo patterns of responses to bronchodilator therapy include a predominant expiratory flow response (left), and a predominant volume response (right)

Despite distinct clinical physiologic features at the time of diagnosis, epidemiologic studies of asthma and COPD have shown that the two diseases over time may develop physiologic features that are quite similar.

The progression in severity of asthma symptoms, the overlap of symptoms seen in some patients with asthma and COPD have lead the group to theorize that asthma may be a risk factor for the subsequent development of COPD.

A prospective observational study.Participants completed up to 12 standard respiratory questionnaires and 11 spirometry lung function measurements over a 20-year period.Survival curves ( with time to development of COPD as the dependent variable) were compared between subjects with asthma and without asthma at the initial survey.

Results:Subjects with active asthma (n=192) had significantly higher hazard ratios than inactive (n=156) or nonasthmatic subjects (n=2751) for acquiring COPD.As compared with nonasthmatics, active asthmatics had a 10-times-higher risk for acquiring symptoms of chronic bronchitis, 17-times-higher risk of receiving a diagnosis of emphysema and 12.5-times-higher risk of fulfilling COPD criteria, even after adjusting for smoking history and other potential confounders

Silva, G. E. et al. Chest 2004;126:59-65Cox survival estimates for CB (top), emphysema (middle), and COPD (bottom) by asthma categories at initial survey adjusted for age, sex, smoking, log IgE, and skin testCumulative survival is much lower for subjects in active asthma categoy

ConclusionsAsthma and COPD share a common background, the differentiation into one disease or the other being modulated by environmental (exposure to allergens, respiratory infections, and smoking) and host factors (AHR, atopy and genetic predisposition).

ConclusionsIt has been suggested that airway inflammation and airflow obstruction seen in asthmatics with increased AHR may lead to subsequent lung remodelling due to airway wall thickening and subepithelial fibrosisThis remodelling could result in irreversible airflow obstruction- AHR is a determinant in COPD?

Remodelling and Inflammation of Bronchi in Asthma and COPD COPDAsthmaIn general there is epithelial fragility and thickening of the reticular basementmembrane, even in mild asthma; increased airway smooth muscle mass, hypertrophy of mucus-secreting glands, increased vascularity, greaqter number of fibroblasts, and increased deposition of collagen in severe asthma and COPD; and mucous metaplasia, squamous metaplasia and parenchymal destruction in COPD

ConclusionsResults from the study of Silva et al show a significant association between an active asthma diagnosis at initial survey and the subsequent development of signs and symptoms consistent with COPD.The mechanism by which asthma may have contributed to this development is still unresolved.

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