Prostaglandin D(2) (PGD(2)) is a major prostanoid, produced mainly by mast cells, in allergic diseases, including bronchial asthma. PGD(2)-induced vasodilatation and increased permeability are well-known classical effects that may be involved in allergic inflammation.

Recently, novel functions of PGD(2) have been identified. To date, D prostanoid receptor (DP) and chemoattractant receptor homologous molecule expressed on T(H)2 cells (CRTH2) have been shown to be major PGD(2)-related receptors. These two receptors have pivotal roles mediating allergic diseases by regulating the functions of various cell types, such as T(H)2 cells, eosinophils, basophils, mast cells, dendritic cells, and epithelial cells.

This review will focus on the current understanding of the roles of PGD(2) and its metabolites in T(H)2 inflammation and the pathogenesis of bronchial asthma.

Ventilator-associated pneumonia (VAP) contributes significantly to morbidity and mortality in critically ill patients, but it can be difficult to diagnose. Clinical criteria, Clinical Pulmonary Infection Score, and quantitative culture of bronchoalveolar lavage have been used to distinguish between patients who are likely positive (sensitivity) and patients who are likely negative (specificity). Despite these test methods, patients continue to be misclassified. False-positive results may lead to inappropriate antibiotic use in patients. For those misclassified as test negative, appropriate treatment may be delayed.

Biomarkers have been suggested as another method to enhance the ability to predict VAP. This article analyzes the evidence for the usefulness of 3 biomarkers that have been proposed as possible biomarkers of VAP: soluble triggering receptor expressed on myeloid type 1 cells, procalcitonin, and C-reactive protein.

METHODS: A Medline search was conducted for the years between 1990 and 2009 to locate articles on the subject of biomarkers for predicting VAP in critically ill adult patients.

RESULTS: Analysis of the literature does not currently support a clinical role for these biomarkers in predicting VAP. Variations in the diagnostic methods, antimicrobial use, cutoff values, and patient populations limit comparisons among the studies.

CONCLUSION: Recommendations are offered to strengthen and standardize methods in future studies to clarify the utility of biomarkers for predicting VAP in specific patient populations.

To review the mechanisms for the perception of dyspnea and to consider the plausibility of interventions that palliate dyspnea after optimal treatment of the underlying disease.

RECENT FINDINGS: Activation of sensory receptors by blood gas abnormalities, mechanical respiratory loads, and hyperinflation provides afferent information to the central nervous system for integration and processing. It has been proposed that a discriminative pathway processes afferent impulses to the somatosensory cortex that reflects the intensity of dyspnea, whereas an affective pathway projects afferent impulses to structures of the limbic system that reflects the unpleasantness of dyspnea. In one study, patients with chronic obstructive pulmonary disease reported consistently higher ratings of breathlessness after administration of naloxone, an opioid receptor antagonist, compared with physiological saline during high-intensity treadmill exercise. This finding supports the role of endogenous opioids in modulating dyspnea. Nebulized furosemide, anti-inflammatory therapy, and chest wall vibration are potential approaches for modulating lung and chest wall receptors to relieve dyspnea.

SUMMARY: Targets for palliating dyspnea in patients with advanced disease include sensory receptors within the lung/chest wall and the central nervous system. The opioid system plays an important role in palliating dyspnea. Both endogenous (β-endorphins) and exogenous (morphine) opioids modulate breathlessness.

Pulmonary arterial hypertension (PAH) is an enigmatic, often fatal disease of the lung. Excess vasoconstriction and progressive obliteration of the precapillary arterioles combine to reduce the cross-sectional area for blood flow and thus cause chronic elevation in the pulmonary arterial pressures with progressive right heart dysfunction, heart failure and death. In 1995, the FDA approved the first therapy for PAH: epoprostenol, a highly efficacious drug but one that was difficult to use for patients and clinicians alike. Since then, there have been eight additional drugs approved, each offering advantages in terms of convenience over previously available drugs. I

n 2009, tadalafil (Adcirca®) was approved for PAH. The 405 patients enrolled in the single pivotal trial give this drug the largest initial placebo-controlled dataset of any of the oral PAH therapies; its once-daily dosing and excellent safety profile make it the most convenient of the therapies by a significant margin. After introducing the PAH disease state with references for more interested readers, this paper discusses the nitric oxide pathway as it relates to the pulmonary circulation, provides an overview of clinically available phosphodiesterase inhibitors and discusses tadalafil in relationship to sildenafil (Revatio®), the first phosphodiesterase inhibitor approved for PAH.