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Exercise-induced anaphylaxis (EIAn) is defined as the occurrence of anaphylactic symptoms (skin, respiratory, gastrointestinal, and cardiovascular symptoms) after physical activity. In about a third of cases, cofactors, such as food intake, temperature (warm or cold), and drugs (especially nonsteroidal anti-inflammatory drugs) can be identified. When the associated cofactor is food ingestion, the correct diagnosis is food-dependent EIAn (FDEIAn). The literature describes numerous reports of FDEIAn after intake of very different foods, from vegetables and nuts to meats and seafood. One of the best-characterized types of FDEIAn is that due to ω5-gliadin of wheat, though cases of FDEIAn after wheat ingestion by sensitization to wheat lipid transfer protien (LTP) are described. Some pathophysiological mechanisms underlying EIAn have been hypothesized, such as increase/alteration in gastrointestinal permeability, alteration of tissue transglutaminase promoting IgE cross-linking, enhanced expression of cytokines, redistribution of blood during physical exercise leading to altered mast-cell degranulation, and also changes in the acid-base balance. Nevertheless, until now, none of these hypotheses has been validated. The diagnosis of EIAn and FDEIAn is achieved by means of a challenge, with physical exercise alone for EIAn, and with the assumption of the suspected food followed by physical exercise for FDEIAn; in cases of doubtful results, a double-blind placebo-controlled combined food-exercise challenge should be performed. The prevention of this particular kind of anaphylaxis is the avoidance of the specific trigger, ie, physical exercise for EIAn, the assumption of the culprit food before exercise for FDEIAn, and in general the avoidance of the recognized cofactors. Patients must be supplied with an epinephrine autoinjector, as epinephrine has been clearly recognized as the first-line intervention for anaphylaxis., Competing Interests: The authors report no conflicts of interest in this work. more...

Background: In patients polysensitized to pollen allergens, the priming effect, by which the sensitivity of the nasal mucosa to an allergen is increased by the previous exposure to another allergen, is a known phenomenon. This study was aimed at evaluating the degree of nasal inflammation, assessed by nasal cytology, in children with allergic rhinitis (AR) from ragweed pollen according to being monosensitized or polysensitized., Methods: The study included 47 children. Of them, 24 suffered from AR caused by sensitization to grass pollen and ragweed pollen (group A) and 23 were sensitized only to ragweed pollen (group B). In all patients, the severity of AR was assessed according to the Allergic Rhinitis and Its Impact on Asthma guidelines, and comorbidities were also evaluated., Results: In group A, 16.7% of children had a mild intermittent AR, 4.2% a moderate-to-severe intermittent, 33.3% a mild persistent, and 45.8% a moderate-to-severe persistent; in group B, 26.1% of children had a mild intermittent AR, 0% a moderate-to-severe intermittent, 52.2% a mild persistent, and 21.7% a moderate-to-severe persistent. No significant difference was detected in the number of the considered comorbidities between the two groups. The cell counts of neutrophils, eosinophils, lymphocytes/plasma cells, and mast cells were high but not significantly different in the two groups., Conclusion: These findings show that the degree of nasal inflammation found in children with ragweed-induced AR is not influenced by additional allergy to grass pollen and confirm the previously reported absence of priming effect in ragweed allergy. more...

β2-agonists were introduced in the 1940s as bronchodilators to be used in obstructive respiratory diseases. Long-acting β2-agonists have been a mainstay of bronchodilating treatment for decades. Recently, agents extending their effect to 24 hours and thus allowing the once-daily administration were introduced, defined as very-long-acting β2-agonists. Olodaterol is a new very-long-acting β2-agonist that has been shown, in controlled trials, to improve lung function as well as clinical outcomes and quality of life. Most of these trials included patients with moderate, severe, or very severe chronic obstructive pulmonary disease (COPD). Olodaterol has a rapid onset of action (comparable to formoterol) and provides bronchodilation over 24 hours. In controlled trials, olodaterol was shown to be as effective as formoterol twice daily, but significantly superior in terms of quality of life in patients with COPD. The safety profile of olodaterol was very good, with a rate of adverse events, including the cardiac events that are particularly important for β2-agonists, comparable to placebo. Also, the efficiency of the Respimat(®) device concurs to the effectiveness of treatment. more...

The current guidelines on chronic obstructive pulmonary disease (COPD) recommend the prominent use of bronchodilators, including long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs), while inhaled corticosteroids are recommended only in patients with severe disease or frequent exacerbations. LABA-LAMA combinations are indicated when single bronchodilators are insufficient to control COPD. A number of LABA-LAMA combinations are available, based on twice-daily or once-daily administration according to the 12- or 24-hour duration of action, respectively. The aclidinium-formoterol combination is based on the new LAMA aclidinium bromide, which has a high selectivity for M3 muscarinic receptors and a fast onset of action, and the well-known LABA formoterol. Both drugs require twice-daily administration. The fixed-dose combination of aclidinium 400 μg/formoterol 12 μg has shown in randomized controlled trials fast and sustained bronchodilation that was greater than either monotherapy and provided clinically significant improvements in dyspnea and health status compared with placebo, also reducing the use of rescue medications. The overall incidence of adverse events was low and comparable to placebo. These data define the aclidinium-formoterol fixed-dose combination as a new treatment option for patients with COPD. The need for twice-daily administration could be an apparent disadvantage compared to the available once-daily LABA-LAMA combinations, but the immediately perceived benefit in reducing dyspnea due to the fast onset of action, as well as reported correct patient use and satisfaction with the Genuair inhaler might prove useful in favoring adherence. more...

Background: House dust mites (HDMs) are a major cause of allergic rhinitis (AR) and asthma worldwide. Recent studies suggested that the allergen load presents seasonal modifications, giving rise to seasonal variation in nasal inflammation and symptoms. The aim of this study was to evaluate by nasal cytology whether nasal inflammation in mite-allergic patients changes with the seasons of the year., Methods: The study included 16 patients (seven males and nine females, mean age 38.1 years) with persistent AR caused by monosensitization to HDMs. Nasal cytology was performed in all patients once monthly for 1 year., Results: Nasal cytology showed that the cells most commonly detected in the nasal mucosa were neutrophils. During the period from October to April, a peak in the number of neutrophils and also the presence of significant numbers of eosinophils, mast cells, and lymphocytes/plasma cells were found, which shows the occurrence of more intense inflammation during these months., Conclusion: Nasal cytology provides useful data in detecting nasal inflammation and its association with the clinical stage of AR. The seasonal variations in nasal cytology are likely to be induced by the fluctuations in the HDM allergen that have been uncovered in recent investigations. more...

Background: An important subpopulation in allergic rhinitis is represented by patients with severe form of disease that is not responsive to drug treatment. It has been reported that grass pollen subcutaneous immunotherapy is effective in drug-resistant patients. In a real-life study, we evaluated the efficacy of 5-grass pollen tablets in patients with grass pollen-induced allergic rhinitis not responsive to drug therapy., Methods: We carried out this multicenter observational study in adults and adolescents with grass-induced allergic rhinitis not responsive to drug therapy who were treated for a year with 5-grass pollen tablets. Clinical data collected before and after sublingual immunotherapy (SLIT) included Allergic Rhinitis and its Impact on Asthma (ARIA) classification of allergic rhinitis, response to therapy, and patient satisfaction., Results: Forty-seven patients entered the study. By ARIA classification, three patients had moderate to severe intermittent allergic rhinitis, ten had mild persistent allergic rhinitis, and 34 had moderate to severe persistent allergic rhinitis. There were no cases of mild intermittent allergic rhinitis before SLIT. After SLIT, 33 patients had mild intermittent allergic rhinitis, none had moderate to severe intermittent allergic rhinitis, seven had mild persistent allergic rhinitis, and seven had moderate to severe persistent allergic rhinitis. The mean medication score decreased from 4.2±1.3 before to 2.4±2.0 after SLIT (P<0.01), representing a reduction of 42%. The response to treatment before SLIT was judged as poor by 70% of patients and very poor by 30%. Patient satisfaction was significantly increased after SLIT (P<0.01)., Conclusion: In real life, most patients with grass pollen-induced allergic rhinitis not responsive to drug treatment can achieve control of the condition with one season of treatment using 5-grass pollen tablets. more...

Noninvasive ventilation (NIV) was introduced as an alternative to invasive mechanical ventilation for acute respiratory failure caused from exacerbations of chronic obstructive pulmonary disease in the 1980s, and its use gradually rose worldwide. Seventy-eight patients (57 males, mean age 78.3 ± 9.2 years) undergoing NIV were evaluated. Of them, 48 (62.3%) had acute hypercapnic respiratory failure because of a chronic obstructive pulmonary disease exacerbation, and the remaining 30 had acute hypercapnic respiratory failure from other causes, mainly cardiac failure. All patients were treated by NIV using the bi-level positive airway pressure set up at high pressure/high backup rate. NIV was successful in 67 subjects (85.9%) and the patients were discharged, 57 of whom continued NIV at home and ten had spontaneous breathing. NIV was unsuccessful in eleven patients, ten of whom died and one was successfully treated by invasive mechanical ventilation. Significant differences were detected for a higher basal Glasgow Coma Scale score in successfully treated patients (P = 0.007), a higher basal Acute Physiology and Chronic Health Evaluation score in unsuccessfully treated patients (P = 0.004), and a lower pH after 1 hour in unsuccessfully treated patients (P = 0.015). These findings show a very high rate of success of NIV in patients with acute hypercapnic respiratory failure not only from chronic obstructive pulmonary disease but also from cardiac failure. This suggests that the use of invasive mechanical ventilation may be further reduced, with a decrease in its known complications as well. more...

Bronchodilators are central drugs in the management of patients with chronic obstructive pulmonary disease (COPD). Indacaterol was the first agent of the novel family of very long-acting β2-agonists to be used as an inhaled bronchodilator for COPD and provides 24-hour therapeutic action, thus allowing once-daily administration. Data from clinical trials show that indacaterol has a bronchodilator effect similar to that of the anticholinergic tiotropium bromide and slightly higher efficacy compared with the long-acting β2-agonists, salmeterol and formoterol. Moreover, the safety profile is excellent and comparable with that of placebo. Concerning adherence with drug treatment and real-life management in respect to long-acting β2-agonists, once-daily dosing makes indacaterol more convenient for COPD patients and is likely to enhance patient adherence. Other very long-acting β2-agonists currently in development include vilanterol, olodaterol, and carmoterol, and these have shown good characteristics for clinical use in the studies reported thus far. more...

Allergic rhinitis is a very common disease affecting about 20% of people. It may be treated by allergen avoidance when possible, by antiallergic drugs such as antihistamines and topical corticosteroids, and by allergen-specific immunotherapy. The latter is the only treatment able to act on the causes and not only on the symptoms of respiratory allergy and is able to maintain its efficacy even after stopping, provided an adequate duration of treatment of 3-5 years is ensured. Sublingual immunotherapy (SLIT) was introduced in the 1990s as a possible solution to the problem of adverse systemic reactions to subcutaneous immunotherapy and has been demonstrated by more than 50 trials and globally evaluated thus far by five meta-analyses as an effective and safe treatment for allergic rhinitis. Life-threatening reactions are extremely rare. However, it is important to note that clinical efficacy occurs only if SLIT meets its needs, ie, sufficiently high doses are regularly administered for at least 3 consecutive years. This is often overlooked in the current practice and may prevent the same success reported by trials from being achieved. more...

Background: Toxocara canis is an intestinal nematode affecting dogs and cats, which causes human infection when embryonated eggs excreted in dog feces are ingested. Humans are paratenic hosts. Although the larvae do not develop into adult worms in the human body, they may migrate to various tissues and organs where they can survive for several years, giving rise to several clinical symptoms, which can present in allergy-like form., Methods: Over 5 years, we examined 9985 patients referred for suspected allergies, based on symptoms such as dermatitis, urticaria, rhinitis, asthma, and conjunctivitis; 753 patients who had allergy tests negative or unrelated to clinical history were tested for seropositivity to T. canis by enzyme-linked immunosorbent assay (ELISA) or Western blotting (WB)., Results: In 240 patients (31.8%), ELISA or WB or both tests were positive for T. canis immunoglobulin G (IgG) antibodies: in particular, 64 of them (26.7%) were positive to ELISA, 110 (45.8%) to WB, and 66 (27.5%) to both tests. Asthma was the most common clinical presentation. Two thirds of patients underwent subsequent anthelmintic therapy and showed a complete remission of symptoms and, in 43% of patients retested by ELISA and WB, became negative to Toxocara., Conclusion: These findings strongly suggest that T. canis plays a significant role in inducing chronic symptoms presenting as suspected allergies. more...

Background: Noninvasive mechanical ventilation (NIMV) is an effective tool in treating patients with acute respiratory failure (ARF), since it reduces both the need for endotracheal intubation and the mortality in comparison with nonventilated patients. A particular issue is represented by the outcome of NIMV in patients referred to the emergency department for ARF and with a do-not-intubate (DNI) status because of advanced age or excessively critical conditions. This study evaluated long-term survival in a group of elderly patients with acute hypercapnic ARF who had a DNI order and who were successfully treated by NIMV., Methods: The population consisted of 54 patients with a favorable outcome after NIMV for ARF. They were followed up for 3 years by regular control visits, with at least one visit every 4 months, or as needed according to the patient's condition. Of these, 31 continued NIMV at home and 23 were on long-term oxygen therapy (LTOT) alone., Results: A total of 16 of the 52 patients had not survived at the 1-year follow-up, and another eight patients died during the 3-year observation, with an overall mortality rate of 30.8% after 1 year and 46.2% after 3 years. Comparing patients who continued NIMV at home with those who were on LTOT alone, 9 of the 29 patients on home NIMV died (6 after 1 year and 3 after 3 years) and 15 of the 23 patients on LTOT alone died (10 after 1 year and 5 after 3 years)., Conclusion: These results show that elderly patients with ARF successfully treated by NIMV following a DNI order have a satisfactory long-term survival. more...

Background: Pulmonary rehabilitation (PR) is recognized as an evidence-based treatment in improving dyspnea and quality of life in patients with COPD. We evaluated the number needed to treat (NNT) to achieve an increase in physical capacity, as defined by a significant improvement in the six-minute walk test (6MWT) in patients with COPD undergoing PR., Methods: The study enrolled 284 patients aged 41 to 86 years (mean age 69.4 years) divided into two groups: a study group (222 patients) undergoing a PR program, and a control group (62 patients) treated only with drugs. The study group included patients with COPD divided in four subgroups according to GOLD stages., Results: In the study group, 142 out of 222 patients (64%) had an increase of at least 54 m in the 6MWT following PR versus 8 out of 62 patients (13%) in the control group after the same time interval. The NNT in the overall study group was 2; the same NNT was obtained in GOLD stages 2, 3, and 4, but was 8 in stage 1., Conclusions: PR is highly effective in improving the exercise capacity of patients with COPD, as demonstrated by a valuable NNT, with better results in patients with a more severe disease. more...

Disease exacerbations are an important aspect of COPD, because they affect its course and are associated with higher lung function decline. On the other hand, data obtained by biopsies have demonstrated that the progression of COPD is related to an increasing impairment of small airways. We sought to evaluate the small airway impairment (FEF25-75) in two groups of COPD patients (each group had 37 subjects) in relation to the frequency of exacerbations and the effectiveness of treatment with tiotropium bromide on the small airway impairment. The mean number of exacerbations was 3.6/year and 1.38/year in frequent and in infrequent exacerbators, respectively (p < 0.001). The mean value of FEF25-75 at baseline was 624 mL and 865 mL in frequent and in infrequent exacerbators respectively (p = 0.002). The changes in respiratory parameters versus baseline showed increases in mean FEV1, FVC, and FEF25-75 in both groups but only the increase in FEF25-75 in frequent exacerbators was statistically significantly (p = 0.013). During the 3-month period of the study the mean number of exacerbations was 0.66 in frequent and 0.12 in infrequent exacerbators. These findings indicate that COPD patients with frequent exacerbations have a higher impairment of small airways. Treatment with tiotropium in COPD subjects with frequent exacerbations proved to be effective in improving small airway impairment. more...

Noninvasive mechanical ventilation (NIMV) is effective in the treatment of patients with acute respiratory failure (ARF). It proved to reduce the need of endotracheal intubation (ETI), the incidence of ETI-associated pneumonia, and mortality compared to nonventilated patients. A particular aspect concerns the outcome of NIMV in patients referring to an emergency room (ER) for ARF, and with a do-not-intubate (DNI) status due to advanced age or critical conditions. The aim of our study is to assess the outcome of NIMV in a group of elderly patients with acute hypercapnic ARF who had a DNI status. An overall number of 62 subjects (30 males, 32 females, mean age 81 +/- 4.8 years, range 79-91 years) referred to our semi-intensive respiratory department were enrolled in the study. The underlying diseases were severe chronic obstructive pulmonary disease (COPD) in 50/62 subjects, restrictive thoracic disorders in 7/62 subjects, and multiorgan failure in 5/62 subjects. Fifty-four/62 patients were successfully treated with NIMV while 2/62 did not respond to NIMV and were therefore submitted to ETI (one survived). Among NIMV-treated patients, death occurred in 6 patients after a mean of 9.9 days; the overall rate of NIMV failure was 12.9%. Negative prognostic factors for NIMV response proved to be: an older age, a low Glasgow Coma Score, a high APACHE score at admission, a high PaCO2 after 12 hours and a low pH both after 1 and 12 hours of NIMV. We conclude that elderly patients with acute hypercapnic ARF with a DNI status can be successfully treated by NIMV. more...