Pulmonary Disease States Associated With Advanced

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Some disorders that involve remodeling of airways and distal lung parenchyma tend to appear with advanced age and become quite prevalent in elderly populations. These disorders include COPD and idiopathic pulmonary fibrosis (IPF). The prevalence of obstructive lung disease is increased in the elderly and may be greatly underestimated in certain elderly populations (Malik et al., 2004; Lundback et al., 2003). Both asthma and COPD

may be considerably underdiagnosed in the elderly (Lebowitz et al., 1975; Janssens et al., 2001), perhaps, in part, due to a decreased ability to perceive an added resistive load such as that caused by bronchoconstriction (Tack et al., 1982).

Airflow obstruction is generally quite reversible in asthmatics with appropriate treatment, which stands in contrast to patients with COPD for whom obstruction is not generally reversible despite therapy. Asthma prevalence in elderly populations may range as high as 8% (Burrows et al., 1991; Parameswaran et al., 1998), and it can be difficult to differentiate from COPD. Older asthmatics with long-standing asthma may have considerable airway remodeling with a prominent component of irreversible airflow obstruction (Finucane et al., 1985), and these individuals often have relatively severe and difficult-to-treat asthma. Some investigators view asthma and COPD as different expressions of one disease entity, a concept that has been named the Dutch hypothesis, because it was first proposed in Groningen in 1961 (Postma and Boezen, 2004). This hypothesis suggests that asthma, chronic bronchitis, and emphysema have various genetic (atopy and airway hyperresponsiveness) and endogenous factors (sex and age) that interact with various exogenous factors (allergens, smoking, pollutants, viral infections) to cause obstructive lung disease (Postma and Boezen, 2004; Bleecker, 2004). However, there are distinct clinical, physiologic, and pathologic characteristics that appear to differentiate asthma from COPD (Fabbri et al., 2003), and patients with fixed airflow obstruction due to asthma tend to have a better response to therapy and better prognosis than patients with COPD (Burrows et al., 1987; Kerstjens et al., 1992).

Chronic obstructive pulmonary disease is the fourth leading cause of death in the United States, and poses a huge economic burden for society (Michaud et al., 2001). Tobacco smoking is the cause of at least 90% of all COPD cases, but other exposures have also been associated with COPD (Barnes, 2000; Fishman, 2005). «j-Antitrypsin deficiency accounts for a about 2% of cases of emphysema (nearly all patients are smokers), and emphysema associated with «^-antitrypsin deficiency is usually diagnosed in the fourth to fifth decade of life (Needham and Stockley, 2004). In contrast, patients with normal «^-antitrypsin levels usually do not develop clinically significant emphysema until they have reached their sixth decade of life. The prevalence of COPD in adults recently was found to be 8.6% in a large survey, and the prevalence in disadvantaged elderly (Malik et al., 2004) or elderly smokers (Lundback et al., 2003) may be considerably higher. A recently published case-control autopsy study showed a prevalence of emphysema or chronic bronchitis of 26.6% for 3,685 patients age 65 or older that were autopsied between 1972 and 1996 (Janssens et al., 2001).

One additional disorder that tends to make its appearance in the elderly is idiopathic pulmonary fibrosis (IPF)

(Coultas et al., 1994). Idiopathic pulmonary fibrosis is characterized by progressive lung remodeling with excess matrix deposition and distortion of lung architecture, which causes a restrictive physiology and impaired gas exchange (Noble and Homer, 2004; Selman and Pardo, 2003). Fortunately, the incidence and prevalence of this progressive disorder, which has a median survival of approximately three years, is much lower than that for asthma and COPD (Coultas et al., 1994; Demedts et al., 2001). Nonetheless, it is estimated that at least 50,000 patients in the United States have this disease, and there are currently no effective therapies that prevent progression to respiratory failure and death (Meyer, 2003).

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