The relationship between marijuana smoking and pulmonary function or respiratory complications is poorly understood; therefore, we conducted a systematic review of the impact of marijuana smoking on ...pulmonary function and respiratory complications. Studies that evaluated the effect of marijuana smoking on pulmonary function and respiratory complications were selected from the MEDLINE, PsychINFO, and EMBASE databases according to predefined criteria from January 1, 1966, to October 28, 2005. Two independent reviewers extracted data and evaluated study quality based on established criteria. Study results were critically appraised for clinical applicability and research methods. Thirty-four publications met selection criteria. Reports were classified as challenge studies if they examined the association between short-term marijuana use and airway response; other reports were classified as studies of long-term marijuana smoking and pulmonary function or respiratory complications. Eleven of 12 challenge studies found an association between short-term marijuana administration and bronchodilation (eg, increases of 0.15-0.25 L in forced expiratory volume in 1 second). No consistent association was found between long-term marijuana smoking and airflow obstruction measures. All 14 studies that assessed long-term marijuana smoking and respiratory complications noted an association with increased respiratory symptoms, including cough, phlegm, and wheeze (eg, odds ratio, 2.00; 95% confidence interval, 1.32-3.01, for the association between marijuana smoking and cough). Studies were variable in their overall quality (eg, controlling for confounders, including tobacco smoking). Short-term exposure to marijuana is associated with bronchodilation. Physiologic data were inconclusive regarding an association between long-term marijuana smoking and airflow obstruction measures. Long-term marijuana smoking is associated with increased respiratory symptoms suggestive of obstructive lung disease.
As HIV-infected persons on combination antiretroviral therapy (ART) are living longer and rates of opportunistic infections have declined, serious non-AIDS-related diseases account for an increasing ...proportion of deaths. Consistent with these changes, non-AIDS-related illnesses account for the majority of ICU admissions in more recent studies, in contrast to earlier eras of the AIDS epidemic. Although mortality after ICU admission has improved significantly since the earliest HIV era, it remains substantial. In this article, we discuss the current state of knowledge regarding the impact of ART on incidence, etiology, and outcomes of critical illness among HIV-infected patients. In addition, we consider issues related to administration of ART in the ICU and identify important areas of future research.
Insulin-like growth factor-I (IGF-I) is a key factor in bone remodeling. In osteoblasts, IGF-I synthesis is enhanced by parathyroid
hormone and prostaglandin E 2 (PGE 2 ) through cAMP-activated ...protein kinase. In rats, estrogen loss after ovariectomy leads to a rise in serum IGF-I and an increase
in bone remodeling, both of which are reversed by estrogen treatment. To examine estrogen-dependent regulation of IGF-I expression
at the molecular level, primary fetal rat osteoblasts were co-transfected with the estrogen receptor (hER, to ensure active
ER expression), and luciferase reporter plasmids controlled by promoter 1 of the rat IGF-I gene (IGF-I P1), used exclusively
in these cells. As reported, 1 μ m PGE 2 increased IGF-I P1 activity by 5-fold. 17β-Estradiol alone had no effect, but dose-dependently suppressed the stimulatory
effect of PGE 2 by up to 90% (ED 50 â¼0.1 n m ). This occurred within 3 h, persisted for at least 16 h, required ER, and appeared specific, since 17α-estradiol was 100â300-fold
less effective. By contrast, 17β-estradiol stimulated estrogen response element (ERE)-dependent reporter expression by up
to 10-fold. 17β-Estradiol also suppressed an IGF-I P1 construct retaining only minimal promoter sequence required for cAMP-dependent
gene activation, but did not affect the 60-fold increase in cAMP induced by PGE 2 . There is no consensus ERE in rat IGF-I P1, suggesting novel downstream interactions in the cAMP pathway that normally enhances
IGF-I expression in skeletal cells. To explore this, nuclear extract from osteoblasts expressing hER were examined by electrophoretic
mobility shift assay using the atypical cAMP response element in IGF-I P1. Estrogen alone did not cause DNA-protein binding,
while PGE 2 induced a characteristic gel shift complex. Co-treatment with both hormones caused a gel shift greatly diminished in intensity,
consistent with their combined effects on IGF-I promoter activity. Nonetheless, hER did not bind IGF-I cAMP response element
or any adjacent sequences. These results provide new molecular evidence that estrogen may temper the biological effects of
hormones acting through cAMP to regulate skeletal IGF-I expression and activity.
Successful treatment of HIV with combination antiretroviral therapy (ART) has resulted in an aging HIV-infected population. As HIV-infected patients are living longer, noninfectious pulmonary ...diseases are becoming increasingly prevalent with a proportional decline in the incidence of opportunistic infections (OIs). Pulmonary OIs such as Pneumocystis jirovecii pneumonia (PCP) and tuberculosis are still responsible for a significant proportion of pulmonary diseases in HIV-infected patients. However, bacterial pneumonia (BP) and noninfectious pulmonary diseases such as chronic obstructive pulmonary disease (COPD), lung cancer, pulmonary arterial hypertension (PAH), and interstitial lung disease (ILD) account for a growing number of pulmonary diseases in aging HIV-infected patients. The purpose of this chapter is to discuss the spectrum and management of pulmonary diseases in aging HIV-infected patients, although limited data exists to guide management of many noninfectious pulmonary diseases in HIV-infected patients. In the absence of such data, treatment of lung diseases in HIV-infected patients should generally follow guidelines for management established in HIV-uninfected patients.
Alveolar destruction is a cardinal feature of emphysema but is not traditionally believed to contribute to the pathogenesis of "classical" asthma. However, the relationship between chronic ...obstructive pulmonary disease (COPD) and asthma is controversial and the variety of mechanisms that can mediate the alveolar destruction in emphysema have not been adequately defined. To address these issues, we used overexpression transgenic approaches to define the effects of Th1/Tc1 and Th2/Tc2 cytokines in the mature murine lung and compared findings in these transgenic systems to the effects of similar interventions after cigarette smoke (CS) exposure. In these experiments, the Th1/Tc1 and Th2/Tc2 cytokines IFN-gamma and interleukin (IL)-13, respectively, both caused emphysema. The IFN-gamma response was associated with neutrophilia but was not associated with mucus metaplasia or a major fibrotic response. In this setting, IFN-gamma was a potent stimulator of matrix metalloproteinases (MMPs), cathepsins, and CXC and other chemokines while inhibiting secretory leukocyte proteinase inhibitor (SLPI). Interestingly, IFN-gamma induced its destructive effects via at least two mechanisms, a CCR5/cathepsin-dependent and apoptosis-mediated pathway and an MMP-12-dependent/apoptosis-independent pathway. CS-induced inflammation, apoptosis, and emphysema were also induced by IFN-gamma- and CCR5-dependent mechanisms. In contrast, IL-13-induced emphysema was associated with eosinophilia, mucus metaplasia, and pulmonary fibrosis. In this setting, IL-13 stimulated MMPs, cathepsins, and a variety of CC chemokines while inhibiting alpha(1)-antitrypsin. A cathepsin-dependent apoptosis pathway also contributed to this remodeling response. Interestingly, abnormalities in vascular endothelial growth factor (VEGF) were also appreciated with VEGF(165) excess producing an asthmalike pulmonary response and IFN-gamma abrogating this response while inducing emphysematous alveolar destruction. These findings provide molecular support for both points of view in the British/Dutch hypothesis controversy regarding the relationship between asthma and COPD. They also highlight the complexity of the pathways that can induce alveolar destruction and suggest that there is a continuum, based on VEGF, between asthma and COPD.
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