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BACKGROUND Nocturnal hypoxemia adversely affects outcomes in patients with cystic fibrosis (CF). Although an early detection of this abnormality may be desirable, still its predictability remains uncertain. The Lung Clearance Index (LCI) is a measure of lung ventilation distribution obtained from a multiple-breath washout technique (MBW), recently implemented in patients with CF. This study aimed to establish whether the LCI predicts nocturnal hypoxemia in patients with stable CF, with mild to moderate disease, and normal diurnal gas exchange. METHODS 31 stable patients (15 males, mean age 17.4 ± 5.2 years) with mild to moderate CF, normoxic when awake, were enrolled. In all patients we performed nocturnal cardio-respiratory polygraphy, lung function measurement, and MBW test to derive LCI values. RESULTS LCI was abnormal in most of the patients and inversely correlated with mean nocturnal SpO2 (r = -0.880 p

The co-existence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), termed the overlap syndrome (OS), has been associated with poorer clinical outcomes, as compared to OSA alone. Multi-morbidity has been shown in both OSA and COPD and may be a putative factor for adverse outcomes in patients with OS. This study aimed to compare the prevalence of co-morbidities and the clinical features in patients with OSA and OS. We analyzed demographic, polygraphic data and co-morbidities from two cohorts of patients, 69 (45 males) with OSA (FVC 94% FEV1 93%) and 79 (65 males) with OS (FVC 82% FEV1 65 %). There were no significant differences between the two groups in demographics (age 67±12 vs 69 ±8, BMI 33.6±6 vs 32±6, OSA vs OS), epworth sleepiness scale (7.7±6 vs 9±4, OSA vs OS) and Mallampati score (3.2±0.1 vs 3.0±01, OSA vs OS.) The two groups had comparable apnea/hypopnea index (AHI) (43.2±21 vs 42.2±21) but different diurnal SaO2 % (94.6 ±1 OSA vs 93.6±2 OS, P

Background and aim. The occurrence of malignant pleural mesothelioma (MPM) has been reported among population groups with no documented professional exposure to asbestos fibres living in different geographic areas. This paper reviews existing data related to non occupational MPM including its occurrence in the province of Catania (Sicily, Italy). Methods. An electronic search of literature related to non occupational MPM was performed including the year 2005. Results. Non occupational MPM in subjects living in areas contaminated by a variety of asbestos and non asbestos fibres has been well documented through a number of epidemiologic studies including cases series, case-control studies, and a cohort study. In addition, the observation of familial clustering of MPM, suggests that genetic factors may play a role in the pathogenesis of this malignancy. The epidemiological evidence also suggests that MPM may occur as a result of the interaction between environmental carcinogens, genetic factors, and virus infection. Conclusion. It is likely that genetic predisposition and non-occupational exposure to low doses of asbestos and asbestos- like fibres may concur to the development of malignant mesothelioma. However, additional epidemiological and laboratory studies are needed to further understand the relationship between environmental exposure and individual susceptibility to this malignancy.

Patients with chronic obstructive pulmonary disease (COPD) are prone to clinical exacerbations that are associated with increased airway inflammation, a potent pro-thrombotic stimulus. Limited information is available on the mechanisms underlying the putative alterations of the endothelial-coagulative system during acute exacerbations. The aim was to investigate whether the activation of the endothelial-coagulative system occurs in association with the acute inflammatory response of COPD exacerbation. We monitored the blood levels of surrogate markers of inflammation: interleukin-6 (IL-6); endothelium damage: von Willebrand’s factor (vWF); clotting activation: D-dimer (D-D), and prothrombin fragment 1+2 (F1+2); fibrinolytic response: plasminogen activator inhibitor 1 (PAI-1), in COPD subjects, during hospital admission and after clinical resolution. In 30 COPD subjects, IL-6, vWF, D-D and F1+2 levels were elevated during exacerbation and decreased significantly at clinical stability (IL-6, p = 0.005; vWF, p < 0.001; D-D, p < 0.001; F1+2, p < 0.001). PAI-1 levels did not change at exacerbation compared to clinically stable situations. Positive correlations were observed between several of the markers measured. Elevation of IL-6, vWF, D-D and F1+2 levels during COPD exacerbations implies a strict association between acute inflammation, endothelial activation and clotting initiation. This was not associated with a change in PAI-1, implying an increase in the fibrinolytic response to inflammation. The pro-thrombotic nature of COPD exacerbations sustained by enhanced clotting activation appears to be mitigated by excessive fibrinolysis.

The sustained imbalance between oxidant and antioxidant species contributes to lung damage in patients with cystic fibrosis (CF). Glutathione (GSH) is an important component of the antioxidant defense in the airways epithelial lining fluid and its transportation out of the cells may be altered in CF. The aim of this study was to assess the oxidants/antioxidants balance in the airways of patients with CF. We measured the concentrations of GSH, the total antioxidant capacity and the concentration of 8-iso-prostaglandin F2α (8-isoprostane), a marker of oxidative stress, in the exhaled breath condensate of 17 non-smoking patients with CF, in stable phase, and in 17 age-matched healthy subjects. The levels of GSH and total antioxidant capacity in patients with CF were significantly lower than in healthy subjects (0.66 ± 0.07 μM versus 1.30 ± 0.08 μM, p < 0.001, respectively for GSH; 0.157 ± 0.02 mM and 0.32 ± 0.01 mM, p < 0.05, respectively for antioxidant capacity). The concentration of 8-isoprostane was higher in CF than in healthy controls (26.5 ± 0.1 pg ml-1 versus 10.8 ± 0.1 pg ml-1; p < 0.05). A low concentration of antioxidant agents, particularly glutathione, and increased levels of 8-isoprostane in the exhaled breath suggest an altered oxidizing environment in the airways of patients with CF. This altered redox environment in the epithelial liquid surface may contribute to progressive lung disease.

Human leukocyte antigen (HLA) phenotype DQ2 is considered the most important genetic marker for un-responsiveness to hepatitis B vaccine. Since celiac disease (CD) is also strongly associated with the same haplo-type it may be hypothesized that celiac patients are less able to respond to the vaccine. We report a retrospective study on celiac patients vaccinated with three doses of 10 microg at 3, 5 and 11 months of age by an intramuscular injection of a recombinant hepatitis B vaccine (Engerix B). We found 30 of 60 celiac patients (50%) unresponsive to vaccination and a significant higher number of responders among patients younger than 18 months at the time of celiac disease diagnosis. Our study confirms that celiac patients have a lower percentage of response to hepatitis B vaccination than healthy subjects. These findings provide useful information to evaluate if current vaccine strategies should be reassessed and if revaccination should be recommended.

Background Previous studies have shown that inhaled heparin attenuated the airway responses to allergen, exercise, and AMP bronchial provocation, possibly through an inhibition of mast cell activation. Objective The aim of this study was to provide the evidence of in vivo inhibition of human mast cell activation by heparin in a noninvasive model. Methods Nine atopic and 6 nonatopic subjects received placebo and unfractionated heparin sodium (5000 IU/mL) 15 minutes before an AMP nasal provocation in a double-blind crossover study design. The nasal lavage was collected from these subjects before or 3, 5, 15, or 30 minutes after the AMP nasal challenge, and concentrations of histamine and tryptase in the nasal lavage were measured. Results AMP nasal provocation produced considerable sneezing and induced a transient increase in histamine and tryptase release, with peak values achieved at 3 to 5 minutes after the challenge in all atopic subjects. Compared with placebo, inhaled heparin significantly attenuated the release of histamine and tryptase induced by AMP challenge ( P =.012 and .004, respectively). Moreover, the AMP-induced sneezing was also inhibited by pretreatment with heparin ( P =.016). In nonatopic subjects, AMP did not induce a significant increase in histamine and tryptase release on placebo-treated or heparin-treated days. Conclusion These data suggest that AMP nasal provocation and AMP bronchial provocation cause mast cell mediator release in a similar fashion. In addition, the data support the hypothesis that inhaled heparin plays a protective role against AMP provocation by inhibition of mast cell activation.

To determine whether nocturnal hypoxaemia contributes to the excessive erythrocytosis (EE) in Andean natives, standard polysomnographies were performed in 10 patients with EE and in 10 controls (mean haematocrit 76.6 +/- 1.3% and 5.4 +/- 0.8%, respectively) living at an altitude of 4,380 m. In addition, the effect of O2 administration for 1 h prior to sleep, and the relationship between the hypoxic/hypercapnic ventilatory response and the apnoea/hypopnoea index (AHI) during sleep were studied. Awake arterial oxygen saturation (Sa,O2) was significantly lower in patients with EE than in controls (83.7 +/- 0.3% versus 85.6 +/- 0.4%). In both groups, the mean Sa,O2 significantly decreased during sleep (to 80.0 +/- 0.8% in EE and to 82.8 +/- 0.5% in controls). The mean Sa,O2 values remained significantly lower in patients with EE than in controls at all times of the night, and patients with EE spent significantly more time than the controls with an Sa,O2 of

We evaluated autonomic cardiovascular regulation in subjects with polycythemia and chronic mountain sickness (CMS) and tested the hypothesis that an increase in arterial oxygen saturation has a beneficial effect on arterial baroreflex sensitivity in these subjects. Ten Andean natives with a Hct >65% and 10 natives with a Hct 65% showed an increased incidence of CMS compared with subjects with Hct

The spasmolytic and anti-spasmogenic activity of β-adrenoceptor agonists on airways smooth muscle is thought to involve activation of the cyclic AMP/cyclic AMP-dependent protein kinase (PKA) cascade. Here we have tested the hypothesis that PKA mediates the anti-spasmogenic activity of isoprenaline and other cyclic AMP-elevating agents in guinea-pig isolated trachea by utilizing a number of cell permeant cyclic AMP analogues that act as competitive ‘antagonists’ of PKA. Anion-exchange chromatography of guinea-pig tracheae resolved two peaks of PKA activity that corresponded to the type I (∼5%) and type II (∼93%) isoenzymes. Pre-treatment of tracheae with zardaverine (30 μM), vasoactive intestinal peptide (VIP) (1 μM) and the non-selective activator of PKA, Sp-8-CPT-cAMPS (10 μM), produced a non-parallel rightwards shift in the concentration-response curves that described acetylcholine (ACh)-induced tension generation. The type II-selective PKA inhibitor, Rp-8-CPT-cAMPS (300 μM), abolished this effect. Pre-treatment of tracheae with Sp-8-Br-PET-cGMPS (30 μM) produced a non-parallel rightwards shift of the concentration-response curves that described ACh-induced tension generation. The selective cyclic GMP-dependent protein kinase (PKG) inhibitor, Rp-8-pCPT-cGMPS (300 μM), abolished this effect. Pre-treatment of tracheae with isoprenaline (1 μM) produced a 10 fold shift to the right of the ACh concentration-response curve by a mechanism that was unaffected by Rp-8-Br-cAMPS (300 μM, selective inhibitor of type I PKA), Rp-8-CPT-cAMPS (300 μM) and Rp-8-pCPT-cGMPS (300 μM). We conclude that the anti-spasmogenic activity of Sp-8-CPT-cAMPS, zardaverine and VIP in guinea-pig trachea is attributable to activation of the cyclic AMP/PKA cascade whereas isoprenaline suppresses ACh-induced contractions by a mechanism(s) that is independent of PKA and PKG. British Journal of Pharmacology (2001) 133, 1201–1212; doi:10.1038/sj.bjp.0704213

8-Iso-prostaglandin F(2 alpha) is present in increased amounts in airway inflammation. 8-Iso-prostaglandin F(2 alpha) constricts the airways via the activation of thromboxane A(2) receptors. However, thromboxane A(2) receptors are also present pre-junctionally on cholinergic nerve terminals innervating guinea pig trachea. We have demonstrated that 8-iso-prostaglandin F(2 alpha) inhibited electrical field stimulation-evoked [3H]acetylcholine release in a concentration-dependent manner, an effect that was not inhibited by the selective thromboxane A(2) receptor antagonist 4(Z)-6-[(2,4,5 cis)2-(2-chlorophenyl)-4-(2-hydroxyphenyl)1,3-dioxan-5-yl]hexenoic acid (ICI 192,605). These data suggest that 8-iso-prostaglandin F(2 alpha) inhibits acetylcholine release through a receptor distinct from the thromboxane A(2) receptor and provides evidence that isoprostanes may have a 'dual' role as both beneficial and deleterious mediators in airway disease.

We investigated the ability of the cannabinoid agonists CP55,940 (CB1/CB2) and anandamide (endogenous cannabinoid) to modulate electrical field stimulation (EFS)-induced acetylcholine (ACh) release from parasympathetic nerve terminals innervating guinea-pig trachea. We assessed whether modulation of transmitter release translated to an impact on functional responses by investigating the effect of these agents on contractile responses evoked by EFS and ACh. Furthermore, we evaluated the ability of these compounds to elicit bronchodilation in pre-contracted guinea-pig tracheal strips. CP55,940 and anandamide significantly inhibited EFS-evoked ACh release (maximal inhibition of 35.1±2.9% and 33.4±6.4% at 1 μM, P

(2008). Safety and Efficacy of Long-Term Treatment with Linezolid in Cystic Fibrosis: Case Report. Journal of Chemotherapy: Vol. 20, No. 3, pp. 399-401.

1 We have demonstrated recently that exogenous prostaglandin E2 (PGE2) inhibits electrical field stimulation (EFS)-induced acetylcholine (ACh) release from parasympathetic nerve terminals innervating guinea-pig trachea. In the present study, we have attempted to characterize the pre-junctional prostanoid receptor(s) responsible for the inhibitory action of PGE2 and to assess whether other prostanoids modulate, at a prejunctional level, cholinergic neurotransmission in guinea-pig trachea. To this end, we have investigated the effect of a range of both natural and synthetic prostanoid agonists and antagonists on EFS-evoked [3H]-ACh release. 2 In epithelium-denuded tracheal strips pretreated with indomethacin (10 μM), PGE2 (0.1 nM–1 μM) inhibited EFS-evoked [3H]-ACh release in a concentration-dependent manner with an EC50 and maximal effect of 7.62 nM and 74% inhibition, respectively. Cicaprost, an IP-receptor agonist, PGF2α and the stable thromboxane mimetic, U46619 (each at 1 μM), also inhibited [3H]-ACh release by 48%, 41% and 35%, respectively. PGD2 (1 μM) had no significant effect on [3H]-ACh release. 3 The selective TP-receptor antagonist, ICI 192,605 (0.1 μM), completely reversed the inhibition of cholinergic neurotransmission induced by U-46619, but had no significant effect on similar responses effected by PGE2 and PGF2α. 4 A number of EP-receptor agonists mimicked the ability of PGE2 to inhibit [3H]-ACh release with a rank order of potency: GR63799X (EP3-selective)>PGE2>M&B 28,767 (EP3 selective)>17-phenyl-ω-trinor PGE2 (EP1-selective). The EP2-selective agonist, AH 13205 (1 μM), did not affect EFS-induced [3H]-ACh release. 5 AH6809 (10 μM), at a concentration 10 to 100 times greater than its pA2 at DP-, EP1- and EP2-receptors, failed to reverse the inhibitory effect of PGE2 or 17-phenyl-ω-trinor PGE2 on [3H]-ACh release. 6 These results suggest that PGE2 inhibits [3H]-ACh release from parasympathetic nerves supplying guinea-pig trachea via an interaction with prejunctional prostanoid receptors of the EP3-receptor subtype. Evidence for inhibitory prejunctional TP- and, possibly, IP-receptors was also obtained although these receptors may play only a minor role in suppressing [3H]-ACh release when compared to receptors of the EP3-subtype. However, the relative importance of the different receptors will depend not only on the sensitivity of guinea-pig trachea to prostanoids but on the nature of the endogenous ligands released locally that have activity on parasympathetic nerves. British Journal of Pharmacology (1998) 123, 1246–1252; doi:10.1038/sj.bjp.0701720

Background — It is well established that a depressed baroreflex sensitivity may adversely influence the prognosis in patients with chronic heart failure (CHF) and in those with previous myocardial infarction. Methods and Results — We tested whether a slow breathing rate (6 breaths/min) could modify the baroreflex sensitivity in 81 patients with stable (2 weeks) CHF (age, 58±1 years; NYHA classes I [6 patients], II [33], III [27], and IV [15]) and in 21 controls. Slow breathing induced highly significant increases in baroreflex sensitivity, both in controls (from 9.4±0.7 to 13.8±1.0 ms/mm Hg, P P r =+0.202, P =0.047). In addition, systolic and diastolic blood pressure decreased in CHF patients (systolic, from 117±3 to 110±4 mm Hg, P =0.009; diastolic, from 62±1 to 59±1 mm Hg, P =0.02). Conclusions — These data suggest that in patients with CHF, slow breathing, in addition to improving oxygen saturation and exercise tolerance as has been previously shown, may be beneficial by increasing baroreflex sensitivity.

Granuloma annulare has been widely described in adults in association with systemic diseases such as type 1 diabetes mellitus. However in childhood this relationship remains unclear. We report the case of an 8-year-old girl, with multiple granuloma annulare as first clinical manifestation of type one diabetes mellitus.

Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, which rapidly leads to chronic respiratory failure requiring mechanical ventilation. Currently, forced vital capacity (FVC) < 50% is considered as physiologic marker for admitting patients to Noninvasive Positive Pressure Ventilation (NPPV) intervention, although it has been recently shown the median survival of patients with baseline FVC < 75% much shorter than median survival of patients with baseline FVC > 75%, independently by any treatment. Aim To assess the role of NPPV in improving outcome of ALS, a retrospective analysis was performed to investigate 1 year survival of ALS patients with FVC < 75% and nocturnal respiratory insufficiency, treated with NPPV, compared to a well-matched population of ALS patients, who refused or was intolerant to NPPV. Methods We investigated seventy-two consecutive ALS patients who underwent pulmonary function test. Forty-four presented a FVC > 75% and served as control group. Twenty-eight patients presented a FVC < 75% and showed, at polysomnography analysis, nocturnal respiratory insufficiency, requiring NPPV; sixteen were treated with NPPV, while twelve refused or were intolerant. Results Increased survival rate at 1 year in patients with FVC < 75% treated with NPPV, as compared to those who refused or could not tolerate NPPV (p = 0.02), was observed. The median rate of decline in FVC% was slower in NPPV patients than in patients who did not use NPPV (95% CI: 0.72 to 1.85; p < 0.0001). Conclusion This report demonstrates that early treatment with NPPV prolongs survival and reduces decline of FVC% in ALS.

Patients with chronic obstructive pulmonary disease (COPD) are prone to clinical exacerbations of their disease and this is known to be associated with increased airway inflammation.[1][1] A prothrombotic condition resulting from the inflammatory activation of the endothelium may well occur during

We investigated the interaction between hypoxia and hypercapnia on ventilation and on cerebro-cardio-vascular control. A group of 12 healthy subjects performed rebreathing tests to determine the ventilatory response to hypoxia, at different levels of carbon dioxide (CO(2)), and to normoxic hypercapnia. Oxygen saturation (SaO(2)), end-tidal CO(2) (et-CO(2)), minute ventilation, blood pressure, R-R interval and mid-cerebral artery flow velocity (MCFV) were continuously recorded. The hypoxic ventilatory response significantly increased under hypercapnia and decreased under hypocapnia (slopes L/min/% Sa O(2): -0.33 +/- 0.05, -0.74 +/- 0.02 and -1.59 +/- 0.3, p < 0.0001, in hypocapnia, normocapnia and hypercapnia, respectively). At similar degrees of ventilation, MCFV increased more markedly during normocapnic hypoxia than normoxic hypercapnia; the slopes linking MCFV to hypoxia remained unchanged at increasing levels of et-CO(2), whereas the regression lines were shifted upward. The R-R interval decreased more markedly during normocapnic hypoxia than normoxic hypercapnia and the arterial baroreflex sensitivity was decreased only by hypoxia. Cardiovascular responses to hypoxia were not affected by different levels of et-CO(2). We conclude that concomitant hypoxia and hypercapnia, while increasing ventilation synergistically, exert an additive effect on cerebral blood flow. Increased sympathetic activity (and reduced baroreflex sensitivity) is one of the mechanisms by which hypoxia stimulates cardiac sympathetic activity.

To the Editor: We would like to congratulate Huszar et al. 1 on their important and meticulous study demonstrating elevated adenosine levels in the exhaled breath condensate of atopic asthmatic subjects compared to nonatopic controls. Their findings are in agreement with and somewhat complementary to previous data obtained from bronchoalveolar lavage fluid of patients with asthma and chronic obstructive pulmonary disease 2, thus adding to the …

Airway epithelial cells from bovine airways can release relaxant factors such as nitric oxide (NO) and prostaglandin E(2) and the removal of airway epithelium results in an increased responsiveness of smooth muscle to spasmogen stimuli. In this study, we assessed whether or not epithelial NO modulates the contractile response of bovine trachea in vitro.Cumulative concentration-response curves to acetylcholine (ACh), histamine (Hist) and 5-hydroxytryptamine (5-HT) were obtained in both intact and epithelium denuded tracheal strips in the presence of indomethacin (10 microM).In intact, but not in epithelium denuded strips, preincubation with the NO synthase inhibitor L-N((G))-Nitro-arginine methyl ester (L-NAME), but not with D-NAME, shifted to the left the concentration-response curve to ACh (pD(2) values in the absence and in the presence of L-NAME were 3.47+/-0.1 and 4.60+/-0.1, respectively; P0.05) and to Hist (pD(2) in the absence and in the presence of L-NAME: 3.89+/-0.1 and 4.54+/-0.1, respectively; P0.05). This effect was reversed by L-arginine (1mM), but not by D-arginine. The contractile response to 5-HT was not affected by L-NAME in either intact or epithelium denuded strips. These data suggest that NO is an epithelial relaxant factor modulating airway cholinergic and histaminergic contraction of bovine trachea and that the activation of the epithelial NO synthase is a mediator-specific process.

To investigate whether breathing more slowly modifies the sensitivity of the chemoreflex and baroreflex.University of Pavia, IRCCS Policlinico S. Matteo.Fifteen healthy individuals.Progressive isocapnic hypoxia and progressive hyperoxic hypercapnia were measured during spontaneous breathing and during a breathing rate fixed at 6 and 15 breaths per minute (b.p.m.).Variations in chemo- and baroreflex sensitivity (by monitoring ventilation, oxygen saturation, end-tidal carbon dioxide, R-R interval and blood pressure) induced by different breathing rates.Breathing at 6 b.p.m. depressed (P0.01) both hypoxic and hypercapnic chemoreflex responses, compared with spontaneous or 15 b.p.m. controlled breathing. Hypoxic and hypercapnic responses during spontaneous breathing correlated with baseline spontaneous breathing rate (r = -0.52 and r = +0.51, respectively; P = 0.05). Baroreflex sensitivity was greater (P0.05) during slow breathing at baseline and remained greater at end rebreathing.Slow breathing reduces the chemoreflex response to both hypoxia and hypercapnia. Enhanced baroreflex sensitivity might be one factor inhibiting the chemoreflex during slow breathing. A slowing breathing rate may be of benefit in conditions such as chronic heart failure that are associated with inappropriate chemoreflex activation.

The novel peptide, nociceptin and the mu-opioid agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) produced a concentration-dependent inhibition of electrical field stimulation (EFS)-evoked release of acetylcholine (ACh) from cholinergic nerves innervating guinea-pig trachea. The non-selective opioid receptor antagonist, naloxone, did not antagonize the inhibitory action of nociceptin under conditions where the inhibition of ACh release evoked by DAMGO was completely reversed. It is suggested that DAMGO and nociceptin can inhibit cholinergic, parasympathetic neurotransmission to the airways via the activation of classical (naloxone-sensitive) and novel (naloxone-insensitive) opioid receptors, respectively.

To the Editor: We read with great interest the article by Luijk et al. 1 describing the time-course of substantial protective effects after a single dose of inhaled fluticasone propionate (FP) on adenosine-5'-monophosphate (AMP)-induced bronchoconstriction in asthma. No change was observed in terms of exhaled nitric oxide (eNO) levels. These findings would further support the current opinion that airway responsiveness to AMP is more sensitive than eNO, together with other noninvasive markers of airway inflammation, in assessing the response to anti-inflammatory treatments 2, 3 …

Rationale Previous studies have shown that inhaled heparin attenuated the airway responses to allergen, exercise and AMP bronchial provocation, possibly through an inhibition of mast cell activation. The objective of the current study was to determine whether inhaled heparin affect the release of mast cell mediators, histamine and tryptase, induced by AMP nasal provocation. Methods Nine atopic and six non-atopic subjects received placebo and heparin (15,000 units USP/mL) 15 min before a AMP nasal provocation in a double blind crossover study design. The nasal lavage was collected from these subjects prior to or 3, 5, 15 or 30 minutes after the AMP nasal challenge, and concentrations of histamine and tryptase in the nasal lavage were measured. Results In atopic subjects, when received placebo, AMP nasal provocation induced a transient increase in the histamine and tryptase release with peak values achieved at 3–5 minutes after the challenge. In comparison, inhaled heparin significantly attenuated the release of histamine and tryptase induced by AMP challenge (p=0.02 and 0.012, respectively). In non-atopic subjects, AMP did not induce a significant increase in histamine and tryptase release in both placebo day and heparin treatment day. Conclusions These data suggest that AMP nasal provocation causes mast cell mediator release in a similar fashion as that induced by AMP bronchial provocation. In addition, the data support the hypothesis that inhaled heparin plays a protective role against AMP provocation by inhibition of mast cell activation.