2). This observation suggests that in some patients and/or in some situations the current dosage based on the stable state nadir plasma levels of heterozygotes or the route of administration may be insufficient to prevent lung deterioration [52] and perhaps bolus or inhaled therapy at the start of an exacerbation might CHIR99021 IC50 prove effective [53]. Clearly further studies are needed to determine the validity of this approach. Figure 2 The decline in FEV1 (l) for a 41 year-old male. Footnote: Between 1980 and 1985 a severe drop in FEV1 from 2.7 to 1.7 liters was noted. Started with augmentation therapy in 1985, the lung function parameters stabilised over a period of approximately … Hospital admissions are expensive and associated with increased mortality in COPD [54,55].

Thus such AATD patients (despite usual COPD preventative therapy) may represent a more immediately cost effective group requiring augmentation therapy and frequency of admissions pre and post therapy can be monitored to indicate probable benefit or lack of benefit. However it may be that local administration of AAT by the inhaled route will prove most effective in frequent exacerbations as these are airway dominant episodes and not alveolar/interstitial processes, that may be beyond the reach of conventional nebulisers [56]. Results of the current ongoing trial in such patients may help resolve this issue [57]. Different series have demonstrated a prevalence of bronchiectasis of around 25% to 50% in patients with AATD [58,59]. The relationship between AATD and bronchiectasis is not fully elucidated.

Although some studies suggest that patients with AATD are more at risk of developing bronchiectasis, large series of bronchiectasis patients have failed to demonstrate an increase of cases with AATD [60]. Moreover, the prevalence of bronchiectasis in patients with airflow obstruction is similar to that seen in usual COPD [61,62]. The presence of bronchiectasis is associated with increased risk of bronchial colonisation and hence airway inflammation, and more frequent and severe exacerbations in usual COPD [62,63]. Therefore, it is likely that AATD patients with infective complications such as frequent exacerbations, bronchiectasis, pneumonia or even chronic bronchitis may represent a subgroup with particular need for acute or long term augmentation therapy [29,33] as illustrated in the case 3 although perhaps again the airway route of administration may be more relevant.

From the criteria for augmentation therapy to a personalised approach to treatment Soon after the Drug_discovery approval of augmentation therapy by the Food and Drug Administration, the scientific societies produced the first guidelines for augmentation, that included the classical criteria for treatment comprising, among others, the demonstration of airflow obstruction, a severe AAT deficiency (usually PI*ZZ or null genotypes), and abstinence of smoking [64].