Bridging Lung Development with Chronic Obstructive Pulmonary Disease. Relevance of Developmental Pathways in Chronic Obstructive Pulmonary Disease Pathogenesis.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation. This generic term encompasses emphysema and chronic bronchitis, two common conditions, each having distinct but also overlapping features. Recent epidemiological and experimental studies have challenged the traditional view that COPD is exclusively an adult disease occurring after years of inhalational insults to the lungs, pinpointing abnormalities or disruption of the pathways that control lung development as an important susceptibility factor for adult COPD. In addition, there is growing evidence that emphysema is not solely a destructive process because it is also characterized by a failure in cell and molecular maintenance programs necessary for proper lung development. This leads to the concept that tissue regeneration required stimulation of signaling pathways that normally operate during development. We undertook a review of the literature to outline the contribution of developmental insults and genes in the occurrence and pathogenesis of COPD, respectively.

Risk factors and early origins of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease is mainly a smoking-related disorder and affects millions of people worldwide, with a large effect on individual patients and society as a whole. Although the disease becomes clinically apparent around the age of 40-50 years, its origins can begin very early in life. Different risk factors in very early life--ie, in utero and during early childhood--drive the development of clinically apparent chronic obstructive pulmonary disease in later life. In discussions of which risk factors drive chronic obstructive pulmonary disease, it is important to realise that the disease is very heterogeneous and at present is largely diagnosed by lung function only. In this Review, we will discuss the evidence for risk factors for the various phenotypes of chronic obstructive pulmonary disease during different stages of life.

Comorbidities associated with psoriasis: an experience from the Middle East.

Recent studies suggest that psoriasis patients have higher rates of comorbidities. We sought to determine the prevalence of comorbidities and co-medications in our psoriasis patients. We conducted case-control study in 1835 patients with psoriasis vulgaris and age- and gender-matched cohort without psoriasis. Patients were examined for clinical characteristics of psoriasis, PASI scores, and data of age, sex, body mass index (BMI), smoking status, comorbidities, and co-medications were analysed for both patients and controls. We identified 1661 (92.8%) patients with mild to moderate psoriasis (PASI < 10) and 129 patient's (7.03%) with severe psoriasis (PASI > 10). Patients with psoriasis were more likely to be current smokers (51.34% vs 32.51% controls). Respective prevalence rates of risk factors in those with mild-moderate psoriasis, severe psoriasis, and controls were as follows: inflammatory arthritis (20%, 31% and 10.68%); coronary heart disease (4.1%, 8.35% and 1.42%); obesity (BM1) (32.5%, 41% and 17%); diabetes mellitus type II (37.4%, 41% and 16%); hypertension (32%, 40.3% and 11.55%); dyslipidemia (14.1%, 22.48% and 4.96%); metabolic syndrome (16%, 26.35% and 6.76%); chronic obstructive pulmonary disease (COPD) (5.36%, 6.98% and 4.03%); cancer (0.3%, 1.55% and 0.16%). They had a higher odds of inflammatory arthritis, coronary heart disease, obesity, diabetes mellitus II, hypertension, dyslipidemia, and metabolic syndrome. They were receiving significantly wider varieties of drugs. Which most commonly included antidiabetic drugs, antihypertensives, and hypolipidemic drugs.

Lung development and susceptibility to chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease with emphysema has been considered to be an accelerated involutional disease of aging smokers. However, because only a proportion ( approximately 15%) of smokers develop chronic obstructive pulmonary disease with emphysema, clearly genetic susceptibility must play a significant part in determining both the age of onset and the rapidity of decline in lung function. In mice, interference with key genes, either by null mutation, hypomorphism, or gain or loss of function, results in phenotypes comprising either neonatal lethal respiratory distress if the structural effect is severe, or reduced alveolarization and/or early-onset emphysema if the effect is milder. Likewise, null mutants that interfere with matrix assembly and/or integrity, such as elastin, lysyl oxidase, or fibrillin, also result in alveolar dysplasia. Importantly, null mutation of Smad3, which encodes a receptor-activated Smad in the transforming growth factor-beta signaling pathway, results in a more subtle failure to correctly organize the alveolar matrix, which is in turn antecedent to early-onset emphysema mediated by matrix metalloproteinase-9. Furthermore, exposure to side-stream smoke profoundly exacerbates and accelerates alveolar destruction, leading to more severe early-onset emphysema in young Smad3-null mice (unpublished data). Interestingly, polymorphisms in the fibrillin, transforming growth factor-beta type II receptor, and matrix metalloproteinase-9 genes have been described in humans with emphysema. Thus, dysplastic or degraded matrix cannot provide the structural niche for alveolar stem/progenitor cells to assume the correct phenotype and/or repair the alveolar cell lineage niche. The hope is that providing the correct exogenous signals can coax them into doing so.