The prevalence and characteristics of pulmonary hypertension in adults with sickle cell disease have not been clearly established.

Inflammation may contribute to the pathogenesis of various forms of pulmonary hypertension (PH). Recent studies in patients with idiopathic PH or PH associated with underlying diseases suggest a role for interleukin-6 (IL-6).

Rationale: Telomere length is considered a marker for biological aging. Chronic obstructive pulmonary disease (COPD) may be associated with premature aging. Objectives: To test the hypothesis that patients with COPD experience accelerated telomere shortening and that inflammation is linked to this process. Methods: We measured telomere length, using a quantitative polymerase chain reaction–based method, and plasma levels of various cytokines in 136 patients with COPD, 113 age- and sex-matched smokers, and 42 nonsmokers with normal lung function. Measurements and Main Results: Median (range) telomere length ratio was significantly lower in patients with COPD (0.57 [0.23–1.18]) than in control smokers (0.79 [0.34–1.58]) or nonsmokers (0.85 [0.38–1.55]) (P < 0.001). The difference remained highly significant when using logistic regression analysis adjusted for age, sex, and tobacco exposure. Both females and males with COPD had shorter telomere length than same-sex control subjects. Telomere length was related to age in patients and control subjects but was shorter in patients than in control subjects in all age groups. No relationship was found between telomere length and tobacco exposure in patients or control subjects, with no difference between control smokers and nonsmokers. In patients with COPD, telomere length was related to PaO2 (P < 0.001) and PaCO2 (P < 0.001) but not to lung function parameters or the BODE Index. Patients with COPD also had elevated plasma levels of various cytokines, interleukin-6 correlating negatively with telomere length (P < 0.001). Conclusions: Given that in vivo telomere length reflects cellular turnover and exposure to oxidative and inflammatory damage, our data support accelerated aging in COPD.

The clinical pulmonary infection score—original or modified—has been proposed for the diagnosis and management of ventilator-associated pneumonia. In 79 episodes of suspected pneumonia, we prospectively assessed the diagnostic accuracy of the physicians' clinical assessment of probability and of the modified clinical pulmonary infection score, both measured before (pretest) and after (post-test) incorporating gram stains results, using bronchoalveolar lavage fluid culture as the reference test. The pretest clinical estimate was inaccurate (sensitivity 50%, specificity 58%); the mean clinical pulmonary infection score at baseline was 6.5 ± 1.3 (range, 3–9) and 5.9 ± 1.7 (range, 3–9), respectively, for the 40 confirmed and the 39 nonconfirmed episodes (p = 0.07), and only slightly more accurate (sensitivity 60%, specificity 59%) than the clinical prediction. Incorporating the gram stain results of either directed or blind protected sampling increased the diagnostic accuracy (sensitivity and specificity of 85% and 49% and 78% and 56%, respectively) of the clinical score and increased the likelihood ratio for pneumonia of a score of more than six from 1.46 to 1.67 and 1.77. The clinical pulmonary infection score has low diagnostic accuracy; however, incorporating gram stains results into the score may help clinical decision making in patients with clinically suspected pneumonia.

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation of unknown pathogenesis. Objectives: To investigate whether telomere dysfunction and senescence of pulmonary vascular endothelial cells (P-ECs) induce inflammation in COPD. Methods: Prospective comparison of patients with COPD and age- and sex-matched control smokers. Investigation of mice null for telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes. Measurements and Main Results: In situ lung specimen studies showed a higher percentage of senescent P-ECs stained for p16 and p21 in patients with COPD than in control subjects. Cultured P-ECs from patients with COPD exhibited early replicative senescence, with decreased cell-population doublings, a higher percentage of β-galactosidase–positive cells, reduced telomerase activity, shorter telomeres, and higher p16 and p21 mRNA levels at an early cell passage compared with control subjects. Senescent P-ECs released cytokines and mediators: the levels of IL-6, IL-8, monocyte chemotactic protein (MCP)-1, Hu-GRO, and soluble intercellular adhesion molecule (sICAM)-1 were elevated in the media of P-ECs from patients compared with control subjects at an early cell passage, in proportion to the senescent P-EC increase and telomere shortening. Up-regulation of MCP-1 and sICAM-1 led to increased monocyte adherence and migration. The elevated MCP-1, IL-8, Hu-GROα, and ICAM-1 levels measured in lungs from patients compared with control subjects correlated with P-EC senescence criteria and telomere length. In Tert−/− and/or Terc−/− mouse lungs, levels of the corresponding cytokines (MCP-1, IL-8, Hu-GROα, and ICAM-1) were also altered, despite the absence of external stimuli and in proportion to telomere dysfunction. Conclusions: Telomere dysfunction and premature P-EC senescence are major processes perpetuating lung inflammation in COPD.