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Since the SARS-CoV-2 pandemic onset, many routine medical activities have been put on hold and this has deeply affected the management of patients with chronic diseases such as obstructive sleep apnea. Untreated OSA is associated with increased mortality and difficulties in social functioning. A delay in initiating treatment may therefore have harmful consequences. Between February and April 2020, the so-called first wave of the pandemic, the overall activity of sleep centers in Europe was reduced by 80%. As the international infection control authorities released guidelines for SARS-CoV-2 outbreak control, many of the national sleep societies provided strategies for a gradual re-opening of sleep facilities. Most of these strategies were not evidences-based and, in a climate of general concern, worldwide it was strongly advised to post-pone any non-urgent sleep-related procedure. Despite the initial idea that the outbreak could be transient, after one year it is still ongoing and the price we are paying, not only includes deaths caused by COVID-19, but also deaths caused by missed or late diagnosis. As further delays in diagnosing and treating patients with sleep apnea are no more acceptable, a new arrangement of sleep facilities and resources, in order to operate safely and effectively, is now mandatory. In this article, we review most recent literature and guidelines in order to provide practical advice for a new arrangement of sleep laboratories and the care of patients with obstructive sleep apnea after one year from the onset of the COVID-19 pandemic.

Objective To evaluate the rate of progression towards specific autoimmune diseases (SADs) of a prospective, multi-centre cohort of patients classifiable as interstitial pneumonia with autoimmune features (IPAF). Methods IPAF patients were enrolled based on specific research criteria, and jointly followed by rheumatologists and pulmonologists for at least one year with clinical check-ups, serological exams including autoimmunity, capillaroscopy and high-resolution computed tomography (HRCT). Diagnostic assessment was repeated at least once a year, or earlier when deemed useful. Results We enrolled 191 IPAF patients through 95 different combinations of IPAF criteria. Of these, 24.1% progressed towards SAD, mainly in connective tissue diseases but also in microscopic polyangiitis. The IPAF patients who progressed were younger than stable IPAF patients (63±10 years vs. 68±9 years, p=0.002) and had a longer follow-up (36.9±18.7 vs. 29.3±15.7 months, p=0.007), but similar severity. No parameters were associated with overall progression, but some parameters were associated with the development of specific diagnoses: Sjögren’s syndrome with positivity for SSA (p=0.007, χ2 7.4); idiopathic inflammatory myopathy with mechanic’s hands (p=

Purpose The coexistence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is known as “overlap syndrome” (OS). Patients with OS are usually older than patients with OSA alone, suffer from more profound oxygen desaturation during the obstructive events often accompanied by sustained nocturnal hypoventilation. Although oxygen-enriched positive airway pressure (PAP) is the treatment of choice in these patients, this therapy is often poorly tolerated particularly by the elderly. The aim of this study was to assess the usefulness of nocturnal oxygen therapy via nasal high flow (NHF-OT) as a possible alternative to PAP in patients with OS. Methods Patients > 65 years old with OS and nocturnal respiratory failure (time spent below SaO2 90% (T90) > 30%) had cardio-respiratory monitoring performed at baseline, during NHF-OT, or during conventional oxygen therapy (COT). Results A total of 40 patients were enrolled in the study. NHF-OT significantly reduced the apnea–hypopnea index (AHI) in all patients compared to baseline and COT. The mean basal AHI was 25.4 ± 8.6. During COT and NHF-OT, the AHI was 19.4 ± 7 and 5.4 ± 4.6, respectively (P 2% was 86.2 ± 2.6 at baseline and at equivalent FiO2 it significantly increased to 91.8 ± 2.4 during COT and to 93.9 ± 2.5 during NHF-OT (P P Conclusions In elderly patients with OS, nocturnal treatment with NHF-OT significantly reduces obstructive episodes and improves oxygenation. As the treatment is generally well tolerated compared to PAP, NHF-OT may be a possible alternative therapy in this subgroup of patients.

Since the SARS-CoV-2 pandemic onset, many routine medical activities have been put on hold and this has deeply affected the management of patients with chronic diseases such as obstructive sleep apnea. Untreated OSA is associated with increased mortality and difficulties in social functioning. A delay in initiating treatment may therefore have harmful consequences. Between February and April 2020, the so-called first wave of the pandemic, the overall activity of sleep centers in Europe was reduced by 80%. As the international infection control authorities released guidelines for SARS-CoV-2 outbreak control, many of the national sleep societies provided strategies for a gradual re-opening of sleep facilities. Most of these strategies were not evidences-based and, in a climate of general concern, worldwide it was strongly advised to post-pone any non-urgent sleep-related procedure. Despite the initial idea that the outbreak could be transient, after one year it is still ongoing and the price we are paying, not only includes deaths caused by COVID-19, but also deaths caused by missed or late diagnosis. As further delays in diagnosing and treating patients with sleep apnea are no more acceptable, a new arrangement of sleep facilities and resources, in order to operate safely and effectively, is now mandatory. In this article, we review most recent literature and guidelines in order to provide practical advice for a new arrangement of sleep laboratories and the care of patients with obstructive sleep apnea after one year from the onset of the COVID-19 pandemic.

High-flow nasal cannula oxygen treatment (HFNC) has several physiological benefits in respiratory failure due to chronic obstructive pulmonary diseases (COPD). In addition, the small positive pressure generated at the naso-pharinx tract may counteract obstructive apneas. This study aimed to evaluate the effect of HFNC in patients with overlap syndrome (OS) consisting in severe COPD and mild-moderate obstructive sleep apnea (OSA). 17 patients (8 males, BMI35±7, age75±9 yrs, FEV1 % 45±12) with OS and chronic or nocturnal respiratory failure were included. Among these, there were also patients with apnea-hypopnea index (AHI) >15 who refused continuous positive pressure ventilation (CPAP). We performed a nocturnal polygraphy at baseline (if not hypoxemic during the day), during conventional oxygen treatment (COT) and during HFNC at the same set FiO2 (mean value 27%). Mean PaO2 or PaCO2 at baseline were 60±8 and 45±5 mmHg. Both treatments improved, to different extent, nocturnal oxygenation, but only HFNC reduced significantly the apnea-hypopnea index (AHI), nocturnal parameters changed as follows: All values with HFNC were significant vs COT and baseline. There was no changes in PaO2 or PaCO2 in the morning after each treatment. We conclude that HFNC oxygen treatment is effective in reducing nocturnal apneas and improving oxygenation in patients with severe COPD and mild-moderate OSA compared to COT. HFNC may also be a chance in patients refusing CPAP.

Introduction: Measles is a contagious disease that re-emerged among young adults as a consequence of suboptimal vaccination coverage. Since in the pre-vaccination era measles affected mainly children, little is known about measles-associated respiratory complications in adults. The aim of this study was to describe clinical and radiological findings in adults affected by measles who developed respiratory complications during a recent measles outbreak. Material and methods: In this retrospective chart review-based study we analyzed data from patients admitted for measles from January to June 2018 to a large tertiary care hospital, in one of the main cities in the south of Italy. This city has been the country’s heart of the epidemic with a high morbidity and mortality rate. Results: Among 177 patients (mean age 26 ± 9 years), only 2 were vaccinated. Thirty patients (16.9%) had signs of pneumonia on chest radiography. Computed tomography scan showed the following abnormalities: centrilobular nodules (63%), ground-glass attenuation (63%), air-space consolidation (36%), pleural effusion (16%) and pneumothorax (10%). Five patients developed severe lung injury and hypoxemia requiring admission to Intensive Care Unit. Two young unvaccinated women with no past medical history died from acute respiratory failure. The death was sudden and unpredictable. Conclusions: Measles-associated pneumonia in unvaccinated young adults can cause severe respiratory impairment and death. Our findings support the need for a mandatory vaccination policy.

COVID-19 pandemic turned the entire health-care system organization upside-down, suspending elective activities and outpatient services. In Italy, we are entering a second phase of the pandemic and several strategies have been developed to "re-open" the country, some businesses, and also health care outpatient activities. This manuscript describes the experience of a Southern Italy Respiratory Unit for safely resuming outpatient respiratory services and preventing COVID-19 transmission.

Although continuous positive air pressure (CPAP) has been used to treat obstructive sleep apnea (OSA) for more than three decades, few studies have reported > 5 years adherence to the treatment. The aim of our study was to assess compliance with CPAP treatment over a long term period ranging from 5 to 20 years. From a database of 650 patients with severe OSA (AHI>30) who started CPAP treatment between 1998 and 2006 we retrospectively collected preliminary data for 105 patients. Demographic and clinical data (e.g. polysomnographic, Epworth Sleepiness Scale) and co-morbidities were available from the database. All patients underwent a telephonic interview to assess the actual use of CPAP, hours of nocturnal treatment, causes of cessation and occurrence of new morbidities during the treatment period. At the beginning of the therapy patients (72% males) had a mean age of 54.9±9.6 yrs, AHI 52.5 ±19.6, BMI 32.2± 6.3 and an Epworth Sleepiness Scale score of 10.9 ±4.6. We found that compliance with CPAP slightly decreased, although remaining quite high, over a long period of time being 94% during the first year, 89% at 5 yrs, 88.7% at 10 yrs, 85.5 % at 15 yrs and 84.3% at 20 yrs. The mean duration of the treatment before suspension was 7.6±4 yrs. The mean rate of nocturnal use did not significantly change over the time and was 7.2 ± 1.9 hours/day at 20 yrs. The long term adherence to CPAP therapy was significantly associated with younger age of the patients, female sex and more severe sleepiness, but not with the severity of OSA. These preliminary data indicate that compliance with CPAP treatment in patients with severe OSA, although a slight decrease through the time, remains high at twenty years follow-up.

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

Regular treatment with inhaled corticosteroids (ICS) is known to reduce airway hyperresponsiveness (AHR) to adenosine 5'-monophosphate (AMP) in asthma even after a single dose of fluticasone propionate (FP).To determine whether this rapid protective effect of a single dose of FP is also present in COPD.23 mild asthmatic and 24 COPD subjects with documented AHR to both AMP and methacholine took part in a randomized, double-blind, placebo-controlled, crossover study to measure AHR to inhaled AMP and methacholine 2 h after either 1000 μg FP or matched placebo.In subjects with asthma, 1000 μg FP in a single dose significantly attenuated the constrictor response to AMP, geometric mean (range) PC20AMP values increasing from a 19.2 (1.3-116.3) to 81.5 (9.6-1600.0) (p0.001; post-placebo vs post-FP) mg/ml. Change in the airways response to inhaled AMP after FP was well within test variability in patients with COPD, with PC20AMP values 59.6 (11.3-183.9) and 76.3 (21.0-445.3) (p = 0.022; post-placebo vs post-FP) mg/ml. Additionally, FP failed to significantly attenuate the bronchial response to methacholine in both asthma and COPD subjects. A change in doubling dilution, between placebo and following a single dose of FP, in AMP had a better sensitivity and specificity of 95.8% and 65.2%, compared to methacholine of 79.2% and 43.5% respectively in delineating between COPD and asthma.A single dose of 1000 μg FP rapidly improves AHR to AMP in asthmatics but not in COPD subjects. This may provide a convenient way by which provocation challenge with inhaled AMP may help in discriminating asthma from COPD.

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.

Obstructive sleep apnea is a common disorder in childhood, particularly in the last decade when an increased prevalence of obesity has been documented. The neurocognitive and behavioral problems associated with this disorder have been known for a long time. However, the increased knowledge of cardiovascular and metabolic complications in adults with sleep apnea has been followed by a better understanding of the systemic effects of upper airway obstruction in children. Obstructive sleep apnea (OSA) has been shown to induce autonomic imbalance in children and to affect blood pressure, cerebral blood flow and cardiac function in an early phase. OSA may also induce chronic systemic inflammation and may contribute to the development of metabolic syndrome in obese children. Very recent research indicates that in children primary snoring, the mildest form of the sleep-disordered breathing spectrum, may also be associated with morbidity. It is, therefore, likely that these respiratory sleep disorders do not simply influence children's' performance in private and social life, but may more seriously affect children's' health. The aim of this review is to outline early systemic complications of obstructive sleep apnea and primary snoring in infants and children.

New emerging infectious diseases include "severe acute respiratory distress syndrome" (SARS) and avian influenza A H5N1. First cases of SARS, induced by a new strain of coronavirus, were described in China in 2002 and by May 2003 8360 cases and 764 deaths were reported by the World Health Organization. The disease can be transmitted from person to person and at the onset is characterized by nonspecific symptoms such as a fever of > 38 degrees C, dry cough, myalgia, and dyspnea. Adults can develop severe hypoxemia requiring intubation, whereas the course of the disease is generally benign in children. Avian influenza A H5N1 is another emerging infectious disease transmitted from avian species to humans, without clear evidence of transmission from human to human. The widespread outbreaks of H5N1 avian influenza in 2003-2004 have caused major problems for the poultry industry in many Asian countries. On January 2004 the disease crossed over to humans, for the first time in Vietnam, causing 74 deaths to date (mortality rate of 50%) in southeastern countries. Unlike SARS, the avian flu occurs in rural areas, where people live in intimate contact with birds, and many of the victims are children < 5 years of age. As for SARS, the World Health Organization has adopted a global action plan to control avian influenza among chickens and ducks and at the same time to limit the threat of a human flu pandemic.

Obstructive sleep apnoea (OSA) is a common disorder characterized by repetitive episodes of nocturnal breathing cessation due to upper airway collapse. OSA causes severe symptoms, such as excessive daytime somnolence, and is associated with a significant cardiovascular morbidity and mortality. Different treatment options are now available for an effective management of this disease. After more than three decades from its first use, continuous positive airway pressure (CPAP) is still recognized as the gold standard treatment. Nasal CPAP (nCPAP) is highly effective in controlling symptoms, improving quality of life and reducing the clinical sequelae of sleep apnoea. Other positive airway pressure modalities are available for patients intolerant to CPAP or requiring high levels of positive pressure. Mandibular advancement devices, particularly if custom made, are effective in mild to moderate OSA and provide a viable alternative for patients intolerant to CPAP therapy. The role of surgery remains controversial. Uvulopalatopharyngoplasty is a well established procedure and can be considered when treatment with CPAP has failed, whereas maxillar-mandibular surgery can be suggested to patients with a craniofacial malformation. A number of minimally invasive procedures to treat snoring are currently under evaluation. Weight loss improves symptoms and morbidity in all patients with obesity and bariatric surgery is an option in severe obesity. A multidisciplinary approach is necessary for an accurate management of the disease.

Adenosine in a signaling nucleoside eliciting many physiological responses. Elevated levels of adenosine have been found in bronchoalveolar lavage, blood and exhaled breath condensate of patients with asthma a condition characterized by chronic airway inflammation. In addition, inhaled adenosine-5'-monophosphate induces bronchoconstriction in asthmatics but not in normal subjects. Studies on animals and humans have shown that bronchoconstriction is most likely due to the release of inflammatory mediators from mast cells. However a number of evidences suggest that adenosine modulates the function of many other cells involved in airway inflammation such as neutrophils, eosinophils, lymphocytes and macrophages. Although this clear pro-inflammatory role in the airways, adenosine may activate also protective mechanisms particularly against lung injury. For many years this dual role of adenosine in the respiratory system has represented an enigma, and only recently it has become clear that biological functions of adenosine are mediated by four distinct subtypes of receptors (A1, A2A, A2B, and A3) and that biological responses are determined by the different pattern of receptors distribution in specific cells. Therefore, pharmacological modulation of adenosine receptors, particularly A2B, may represent a novel therapeutic approach for inflammatory diseases. Moreover, as bronchial response to adenosine strictly reflects airway inflammation in asthma, bronchial challenge with adenosine is considered a valuable clinical tool to monitor airway inflammation, to follow the response to anti-inflammatory treatments and to help in the diagnostic discrimination between asthma and chronic obstructive lung disease.

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

Purpose of review There is evidence that bronchial hyperresponsiveness to inhaled adenosine may be a better marker of airway allergic inflammation than bronchial hyperresponsiveness to other spasmogens. Here the authors review the most recent development in this area of rapidly evolving clinical research, focusing on the putative role of adenosine as a useful bronchoprovocant in asthma. Recent findings New studies have provided evidence that hyperresponsiveness to AMP strongly correlates with sputum, blood/bronchial tissue eosinophilia and exhaled nitric oxide, whereas hyperresponsiveness to methacholine is related to changes in forced expiratory volume in 1 s, thus reflecting changes in airway caliber and functional state. Other recent studies have emphasized that the state of atopy is critically important in the bronchial response to inhaled AMP. The early finding that in people with asthma treatment with inhaled glucocorticosteroids significantly reduces airway responsiveness to AMP, as compared with other spasmogens such as methacholine or bradykinin, has been confirmed by recent reports which have also outlined that this is an early phenomenon. Summary Taken together these studies evidence that hyperresponsiveness to inhaled adenosine may be a better marker of airway allergic inflammation than hyperresponsiveness to other spasmogens. This peculiar property of adenosine suggests that bronchial provocation with inhaled adenosine could provide a reliable noninvasive tool for monitoring asthma activity/progression, and assessing the response to antiinflammatory treatments.

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

Allergen immunotherapy is a disease-modifying therapy, effective for the treatment of allergic rhinitis, allergic asthma, conjunctivitis or stinging insect allergy. Allergen immunotherapy involves the administration of increasing doses of allergens with the aim of ameliorating the allergic response. Although precise underlying mechanisms of the induction of immune tolerance remain unclear, immunotherapy has been associated with the induction of distinct subsets of Tregs that eventually lead to peripheral tolerance by inducing a deviation from Th2 to Th1 immune responses. This review focuses on the current knowledge of the mechanisms of immunotherapy in relationship to different routes of administration and also provides a unifying view.

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

Respiration is a powerful modulator of heart rate variability, and of baro- and chemoreflex sensitivity. Abnormal respiratory modulation of heart rate is often an early sign of autonomic dysfunction in a number of diseases. In addition, increase in venous return due to respiration may help in maintaining blood pressure during standing in critical situations. This review examines the possibility that manipulation of breathing pattern may provide beneficial effects in terms not only of ventilatory efficiency, but also of cardiovascular and respiratory control in physiologic and pathologic conditions, such as chronic heart failure. This opens a new area of future research in the better management of patients with cardiovascular autonomic dysfunction.

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.