The results of this analysis were consistent with a delayed diagnosis of alpha-1 antitrypsin deficiency being associated with worse COPD-related symptoms and functional status, and with a trend toward worsened air-flow obstruction.
Our findings highlight the similarities in the pathophysiology of COPD in individuals with and without AATD, adding a potentially important step to the mechanism of COPD.
We sought to identify subgroups characterized by upper-lobe or lower-lobe emphysema predominance and comparable amounts of total emphysema by analyzing data from 9,210 smokers without alpha-1-antitrypsin deficiency in the Genetic Epidemiology of COPD (COPDGene) cohort.
The intravenous augmentation treatment and lung density in severe alpha-1 antitrypsin deficiency (RAPID) study shows a correlation of an anatomic index of COPD (on CT imaging) correlating with a chemical indicator of matrix injury in COPD, DI.
Notably, 68% of AATD and 65% of COPD responded well with a clinically relevant 6MWD improvement of ?30 m. The improvement in 6MWD was independent of gender, age, pack years, SF36 mental score and body mass index.
Direct and indirect costs (based on self-reported information on healthcare utilization) and health-related quality of life (HRQL, as assessed by SGRQ, CAT, and EQ-5D-3 L) were compared between 131 AATD patients (106 with, 25 without augmentation therapy (AT)) and 2,049 COPD patients without AATD participating in the COSYCONET COPD cohort.
Long-term clinical outcomes following treatment with alpha 1-proteinase inhibitor for COPD associated with alpha-1 antitrypsin deficiency: a look at the evidence.
In severe COPD-AATD patients, we found 205 differentially expressed genes (DEGs) (114 upregulated and 91 downregulated) and 28 miRNA (20 upregulated and 8 downregulated) compared to patients with mild COPD-AATD disease.
Genetics is a promising area to elucidate pathophysiology and treatment for asthma and COPD, but currently alpha-1 antitrypsin deficiency is the only genetically-determined phenotype that has relevance for COPD management.
Genome-wide association studies and integrative genomics approaches in COPD have demonstrated significant associations with SNPs in the chromosome 15q region that includes CHRNA3 (cholinergic nicotine receptor alpha3) and IREB2 (iron regulatory binding protein 2).We investigated whether SNPs in the chromosome 15q region would be modifiers for lung function and COPD in AAT deficiency.
Although much remains to be done, recent advances and the advent of new methodologies are promising and should yield increased understanding of the genetic and epigenetic mechanisms influencing the pathogenesis of COPD, both related and unrelated to severe AAT deficiency.
Correction for ascertainment and consideration of gene-by-smoking interactions will be crucial for the identification of genes that may modify susceptibility for COPD in families with AAT deficiency.
However, the frequency was significantly increased (0.44) in patients with AAT deficiency (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.17 to 3.72 compared to control subjects; and OR, 2.41; 95% CI, 1.27 to 4.59 compared to COPD).
A recent evidence-based review has offered testing recommendations for AAT deficiency and includes the recommendation that all patients with COPD be tested for AAT deficiency.
At present, most of the genes that contribute to the genetic component to COPD are unknown. alpha 1-Antitrypsin deficiency is clearly a risk factor for COPD, but the other genetic associations with this disease must be considered as tentative.