Airway inflammation in obstructive sleep apnea: Is leptin the missing link?

SummaryBackgroundLocal and systemic inflammation is implicated in the pathophysiology of Obstructive Sleep Apnea (OSA). Exhaled breath condensate (EBC) is a non-invasive sampling method for the lower airways. However, it is important to consider the potential effect of the systemic origin whereas systemic inflammation is significantly elevated. This prospective study was designed to investigate whether airway inflammation is significantly related to plasma leptin levels in OSA patients. Simultaneously, it was designed to investigate whether inflammatory variables predict parameters expressing disease severity and finally whether smoking habit affect the above measurements.Patients & MethodsAbout 45 OSA patients (mean AHI 40±25, 28 smokers) and 25 healthy controls (AHI<5, 15 smokers) were studied and underwent overnight diagnostic polysomnography. We measured pH, 8-isoprostane, TNF-α and IL-6 in EBC and leptin in plasma. Plausible associations between leptin and inflammatory parameters were analyzed after adjustment for proper variables. Similar associations between inflammatory variables and parameters of disease severity were also performed.ResultsAn increased level of leptin and respective increase of inflammatory variables was found. No significant association was observed between parameters of EBC and plasma leptin levels. A part of the parameters of disease severity is significantly associated with pH and 8-isoprostane. Smoking did not seem to be a critical confounding factor for evaluation of the above measurements.ConclusionsIncreased levels of leptin were not associated with the observed airway inflammation in OSA. The observed airway inflammation seemed to be independent of smoking habit with limited association with disease severity

Clinical review: Idiopathic pulmonary fibrosis acute exacerbations - unravelling Ariadne's thread

Idiopathic pulmonary fibrosis (IPF) is a dreadful, chronic, and irreversibly progressive fibrosing disease leading to death in all patients affected, and IPF acute exacerbations constitute the most devastating complication during its clinical course. IPF exacerbations are subacute/acute, clinically significant deteriorations of unidentifiable cause that usually transform the slow and more or less steady disease decline to the unexpected appearance of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) ending in death. The histological picture is that of diffuse alveolar damage (DAD), which is the tissue counterpart of ARDS, upon usual interstitial pneumonia, which is the tissue equivalent of IPF. ALI/ARDS and acute interstitial pneumonia share with IPF exacerbations the tissue damage pattern of DAD. 'Treatment' with high-dose corticosteroids with or without an immunosuppressant proved ineffective and represents the coup de grace for these patients. Provision of excellent supportive care and the search for and treatment of the 'underlying cause' remain the only options. IPF exacerbations require rapid decisions about when and whether to initiate mechanical support. Admission to an intensive care unit (ICU) is a particular clinical and ethical challenge because of the extremely poor outcome. Transplantation in the ICU setting often presents insurmountable difficulties

CD8+ T lymphocytes in bronchoalveolar lavage in idiopathic pulmonary fibrosis

<p>Abstract</p> <p>Background</p> <p>Recently it was shown that in Idiopathic Pulmonary Fibrosis (IPF) tissue infiltrating CD₈₊T lymphocytes (TLs) are associated with breathlessness and physiological indices of disease severity, as well as that CD₈₊TLs recovered by bronchoalveolar lavage (BAL) relate to those infiltrating lung tissue. Since BAL is a far less invasive technique than tissue biopsy to study mechanisms in IPF we further investigated the usefulness offered by this means by studying the relationship between BAL macrophages, neutrophils, eosinophils, CD₃₊, CD₄₊, CD₈₊, CD_8+/38+TLs and CD₄₊/CD₈₊ratio with breathlessness and physiological indices.</p> <p>Patients and methods</p> <p>27 IPF patients, 63 ± 9 years of age were examined. Cell counts were expressed as percentages of total cells and TLs were evaluated by flow cytometry. FEV₁, FVC, TLC, RV, <it>D</it>LCO, PaO₂, and PaCO₂were measured in all. Breathlessness was assessed by the Medical Research Council (MRC) chronic dyspnoea scale.</p> <p>Results</p> <p>CD₈₊TLs correlated positively (r_s= 0.46, p = 0.02), while CD₄₊/CD₈₊ratio negatively (r_s= -0.54, p = 0.006) with the MRC grade. CD₈₊TLs correlated negatively with RV (r_s= -0.50, p = 0.017). CD_8+/38+TLs were negatively related to the FEV₁and FVC (r_s= -0.53, p = 0.03 and r_s= -0.59, p = 0.02, respectively). Neutrophils correlated positively with the MRC grade (r_s= 0.42, p = 0.03), and negatively with the <it>D</it>LCO (r_s= -0.54, p = 0.005), PaO₂(r_s= -0.44, p = 0.03), and PaCO₂(r_s= -0.52, p = 0.01).</p> <p>Conclusion</p> <p>BAL CD₈₊TLs associations with physiological and clinical indices seem to indicate their implication in IPF pathogenesis, confirming our previous tissue study.</p

Early apoptosis of blood monocytes in the septic host: is it a mechanism of protection in the event of septic shock?

INTRODUCTION: Based on the central role of the triggering of monocytes for the initiation of the septic cascade, it was investigated whether apoptosis of blood monocytes in septic patients is connected to their final outcome. METHODS: Blood monocytes were isolated from 90 patients with septic syndrome due to ventilator-associated pneumonia on days 1, 3, 5 and 7 from the initiation of symptoms. Apoptosis was defined after incubation with annexin-V-fluorescein isothiocyanate and propidium iodine and reading by a flow cytometer. The function of first-day monocytes was evaluated from the concentrations of tumour necrosis factor alpha (TNFα) and IL-6 in supernatants of cell cultures after triggering with endotoxins. TNFα, IL-6 and IL-8 were estimated in serum by an enzyme immunoassay. RESULTS: Mortality rates of patients with apoptosis ≤50% compared with patients with apoptosis >50% were 49.12% and 15.15%, respectively (P < 0.0001). Kaplan-Meier analysis showed a 28-day survival benefit in patients with septic shock and monocyte apoptosis >50% compared with those patients with apoptosis ≤50% (P = 0.0032). Production of IL-6 by monocytes on the first day by patients with apoptosis ≤50% was similar compared with monocytes isolated from healthy controls. Serum concentrations of TNFα were higher in patients with monocyte apoptosis ≤50% and septic shock compared with patients with apoptosis >50% on day 7; similar findings occurred for serum IL-6 on days 1 and 7 and for serum IL-8 on days 1 and 5. CONCLUSION: Early apoptosis of monocytes upon presentation of clinical signs of sepsis is connected to a favourable outcome. These findings are of particular importance for the patient with septic shock, where they might constitute a mechanism of pathogenesis