Comparing the compliance to a short schedule of subcutaneous immunotherapy and to sublingual immunotherapy during three years of treatment.

BACKGROUND: Allergen immunotherapy (AIT) in its two forms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) is an effective treatment of respiratory allergy, but is particularly concerned by the issue of compliance. OBJECTIVE: We aimed a real-life study at evaluating the compliance to SLIT and to SCIT administered by a short-course of four injections during a 3-year period of observation. METHODS: A group of 145 patients (79 males, 66 females, age ranging from 14 to 69 years), suffering from pollen-induced rhino-conjunctivitis with or without asthma, were included in the study. Following adequate education on AIT and according to patient's preference, 72 patients chose to be treated with short-course SCIT and 73 chose to be treated with SLIT. The latter was performed by allergen extracts from different manufacturers according to the suggested schedules. RESULTS: The rate of withdrawal was as follows: after one year, 15.6% for SCIT and 33.4 for SLIT; after two years, 25.6% for SCIT and 44.8% for SLIT; after three years, 26.7 for SCIT and 46% for SLIT. There was no significant difference in the rate of withdrawal between males and females. Regarding the safety, no systemic reaction requiring medical treatment was observed either in SCIT or SLIT group. CONCLUSION: The findings of this study confirm that involving the patient in the choice of the route of administration is associated to a satisfactory compliance to AIT. In particular, more than 70% of patients treated with a short schedule of SCIT completed the three-years course of treatment that is recommended for AIT, while this goal was reached by 54% of SLIT treated patients.

Effects of pulmonary rehabilitation on lung function in chronic obstructive pulmonary disease: the FIRST study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) causes an impairment of respiratory function, well reflected by the progressive decrease in forced expiratory volume in 1 second (FEV1). The only interventions able to slow down the FEV1 decline are smoking cessation and drug treatment. Pulmonary rehabilitation (PR), is claimed to improve exercise tolerance, symptoms and quality of life, but its effects on lung function have been scantly investigated. AIM: The aim of this paper was to evaluate, by the study named "FEV1 as an Index of Rehabilitation Success over Time" (FIRST), the effects of PR on lung function in patients with COPD, under drug treatment with inhaled corticosteroids or long-acting ß2-agonists and/or tiotropium in various combinations, according to guidelines, during a 3-year period. DESIGN: Observational, prospective, with two parallel groups study. SETTING: PR setting in an urban hospital. POPULATION: Two hundred fifty-seven COPD patients, 190 (103 males, mean age 71.1 ± 7.1 years range 57-86 years) underwent PR and 67 (49 males, mean age 67.9 ± 7.9 years, range 58-79 years) were treated only with drugs. METHODS: Lung function was measured at baseline and at one-year intervals up to 3 years. The postbronchodilator FEV1 was used for statistical analysis. RESULTS: In the PR group, FEV1 increased from 1240 mL (57.3% of predicted value) to 1252.4 mL (60.8%) after 3 years, whereas in the controls the values were 1367 mL (55% of predicted) at baseline and 1150 mL (51%) after 3 years. This difference was statistically significant (P<0.001). CONCLUSION: In patients with COPD on standard pharmacotherapy, PR significantly affected the decline of FEV1 over time. CLINICAL REHABILITATION IMPACT: The ability to substantially stop the FEV1 decline seems exclusive of PR when added to drug treatment. This finding warrants confirmation from randomized trials.

Ultra short pre-seasonal subcutaneous immunotherapy and pre-coseasonal sublingual immunotherapy for pollen allergy: an evaluation of patient's preference in real life.

BACKGROUND: Specific immunotherapy (SIT) efficacy and safety by subcutaneous (SCIT) and sublingual (SLIT) route is supported by literature data. Pre-coseasonal treatment is currently the more accepted option for pollen immunotherapy in terms of costs and patient's compliance. This retrospective study evaluated the patient's preference concerning subcutaneous or sublingual route in pre-coseasonal treatment. MATERIALS AND METHODS: We evaluated 145 patients (79 males, 66 females, age ranging from 14 to 69 years), suffering from moderate-severe rhino-conjunctivitis or mild bronchial asthma and with homogeneous characteristic according to allergic disease severity. We proposed either SLIT, with extracts by different producers, or SCIT with Pollinex 4 (Allergy Therapeutics, Worthing, UK), a product designed for ultra-short administration in 4 injections, highlighting for each kind of SIT the major practical advantages or burdens. RESULTS: Of 145 patients, 72 chose Pollinex 4 SCIT and 73 chose SLIT. SCIT-treated patients received a total of 90 vaccines (18 patients had double course of SCIT). SLIT-treated patients received a total of 87 vaccines (14 patients had double course of SLIT). In the SCIT group, there were 49 males and 23 females; in the SLIT group, there were 30 males and 43 females. Mean age was 36.5 years in SCIT group and 28.5 years in SLIT group. Males preferred SCIT (49 of 72 patients) and females preferred SLIT (43 of 73 patients). No severe reaction was observed either in SCIT or SLIT group. CONCLUSION: Patients are active subjects in decisional process. Trying to apply in real life the indications coming from guidelines about patient's preference is an important matter. In our patients SCIT with ultra short schedule and SLIT are similarly preferred.

Role of noninvasive ventilation in elderly patients with hypercapnic respiratory failure.

The effectiveness of non-invasive ventilation (NIV) in treating patients with acute respiratory failure (ARF) is showed by its ability to diminish the recurrence to endotracheal intubation (ETI), the occurrence of ETI-associated lung infections as well as related mortality. A specific issue is the outcome of NIV in patients referring to Emergency Department for ARF who receive a do-not-intubate (DNI) order because of too critical conditions or advanced age. Recent data show that elderly patients (mean age 81 years) with ARF who have a DNI order can be successfully treated by NIV, as demonstrated by a survival rate of 83%. The positive outcome was confirmed by a subsequent 3-year observation, that demonstrated an overall survival rate of 54%. These findings clearly suggest to treat by NIV elderly patients also in presence of a DNI order.

[Pulmonary rehabilitation: pathophysiology, indications, and clinical efficacy]. / La riabilitazione in pneumologia: fi siopatologia, indicazioni ed effi cacia clinica.

Pulmonary rehabilitation (PR) is a non pharmacologic treatment of demonstrated efficacy indicated for symptomatic patients with chronic lung diseases. In the pulmonary rehabilitation programs (PRPs), exercise training is a cornerstone component, recommended for improving muscle function. Its aim is to address the disability, intended as the reduction in functional performance and quality of life, derived from muscle deconditioning caused by physical inactivity due to chronic breathlessness, fatigue, and impairment of daily activities claimed by patients with chronic pulmonary diseases. Other components of PRPs are educational, psychosocial and nutritional interventions. Moreover, any PRP should include an outcome assessment, needed for an objective evaluation of program effectiveness, and of patient progress through the time. Although its pivotal role is now accepted worldwide, this was not the prevailing thought during the 1980's and the 1990's, when the pathophysiologic rationale of PR was still not demonstrated, condemning it to be an ancillary treatment to add to standard COPD treatment. The following ascent of PR was mainly due to the number of studies providing its effectiveness, overcoming skepticism and convincing physicians and institutions about its efficacy. Today PR clearly improves exercise tolerance, dyspnea, and quality of life, but despite such demonstration, it is mostly overlooked by health professionals, and only about 2% of patients with COPD undergo to PRPs. A proper consideration of the capability of PR is warranted to ensure optimal management of COPD when the disease causes symptoms and a decrease in physical capacity.

Sublingual immunotherapy in polysensitized patients: effect on quality of life.

BACKGROUND: Quality of life (QOL) is an important issue in allergic rhinitis and has been evaluated in a number of studies that have shown how it is impaired in untreated patients and improved by effective treatment. However, there are no data concerning QOL after sublingual immunotherapy (SLIT) in polysensitized patients. OBJECTIVE: To evaluate the effect, in real-life clinical practice, of SLIT on QOL in a population of polysensitized patients with allergic rhinitis. METHODS: We prospectively evaluated 167 consecutively enrolled polysensitized patients with allergic rhinitis. QOL was measured in all cases with the Rhinoconjunctivitis Quality of Life Questionnaire at baseline and after 1 year of SLIT (performed in approximately 70% of cases using single allergen extracts provided by the same manufacturer). RESULTS: The most frequent causes of sensitization were grass pollen, Parietaria, and house dust mites. The mean number of sensitizations per patient was 3.65. SLIT was performed with 1 extract in 123 patients (73.6%), with 2 extracts in 31 patients (18.6%), and with more than 2 extracts in 13 patients (7.8%). The mean values of all the QOL items improved significantly (P < .01 in all cases), with the following reductions noted: activities, 3.96 to 2.89; sleep, 2.07 to 1.56; general problems, 2.16 to 1.5; practical problems, 3.69 to 2.58; nasal symptoms, 3.57 to 2.50; eye symptoms, 2.92 to 1.83; and emotional aspects, 2.2 to 1.44. CONCLUSIONS: This study provides evidence that QOL can be improved in polysensitized patients treated with SLIT, and that the use of just 1 or 2 allergen extracts seems to be sufficient and effective in terms of improving QOL.

Sublingual immunotherapy: administration, dosages, use.

Allergen extracts for sublingual immunotherapy (SLIT) are currently marketed by several manufacturers, with administration schedules and amount of allergen(s) quite variable in the different products, although almost all are standardized biologically or immunologically. The allergen extracts for SLIT are available in two main pharmaceutical forms: solution to be delivered by drop-counters, pre-dosed actuators (mini-pumps) or disposable single-dose vials; tablets with appropriate composition that allows a slow (1-2 minutes) dissolution in the mouth in contact with saliva. In Europe, SLIT is prescribed in general for one or a few allergens, and mixtures are less used, though there is no immunological contraindication to give multiple allergens. SLIT traditionally involves a build-up phase and a maintenance phase with the top dose. The build-up phase has usually the duration of 4 - 6 weeks. The patient must start with the lowest concentration and gradually increase, using the different dosage preparations, until the maintenance dose is reached. Rush and ultra-rush inductions have been introduced, based on the safety profile of SLIT that is very favorable. For these reasons it has been suggested that an updosing phase maybe even not necessary. The no-updosing approach would result in a treatment that is more patient-friendly and convenient to manage. Indeed, the most recent randomized trials were performed with the no-updosing regimen and their results in term of safety were as favorable as the studies performed with the traditional updosing approach. The currently recommended duration of SLIT is comprised between 3 and 4 years depending on the clinical response in single patients.

Effectiveness of omalizumab in a patient with severe asthma and atopic dermatitis.

The anti-IgE antibody omalizumab is currently indicated in severe asthma not controlled by standard drug therapy. Recently, new indications for omalizumab were suggested, which include atopic dermatitis (AD), a skin disorder characterized by elevated levels of IgE. We report the case of a 39-year old woman with severe asthma and severe AD, both resistant to conventional drug treatment. The patient had a IgE level of 1304 kU/L, which exceeded the recommended maximum level for treating asthma with omalizumab (stated in 700 Ku/L) but was far lower than previously reported in cases of AD treated with anti-IgE. The treatment consisted of a dose of omalizumab 375 mg every two weeks, and induced a rapid improvement of asthma, with no need of other drugs after three months, along with a progressive decline of severity of AD, which after five months was completely cured. These findings suggest the usefulness of omalizumab in patients with concomitant severe asthma and AD, also considering the pharmaco-economic balance obtained by withdrawing the multiple drugs used to treat both diseases.

[A survey on current attitudes to smoking in health care workers in Italy]. / Indagine sull'atteggiamento attuale verso il fumo di sigaretta degli operatori sanitari in Italia.

BACKGROUND: Prevalence of smoking among healthcare workers has been steadily decreasing in recent years but is still higher than in the general population. This may have a negative impact in the process of recognizing smoking as the major avoidable cause of morbidity and mortality. OBJECTIVES: In this study we evaluated the prevalence and the attitudes to smoking in healthcare workers, divided into inpatient and outpatient staff in order to assess the possible role of stress in favouring smoking. METHODS: A standardized questionnaire on smoking was submitted to all employees of the "Istituti Clinici di Perfezionamento", a public hospital in Milan, Italy, covering 1597 subjects. RESULTS: An overall number of 383 subject (24%) answered the questionnaire. Thirty (7.8%) were non-smokers and not exposed to second-hand smoking, 175 (45.7%) were non-smokers but exposed to second-hand smoking, 79 (20.6%) were ex-smokers, and 99 (25.8%) were current smokers. The comparison between inpatient and outpatient staff did not reveal any significant diferences. As to smoking attitudes, 29 subjects (29.3%) were not interested in quitting, 26 (26.3%) tried unsuccessfully to quit, 27 (27.3%) believed they could succeed in quitting, and 17 (17.2%) wanted to quit but did not know how. Also in this case there were no significant differences between inpatient and outpatient staff. CONCLUSION: These findings confirm the decrease in the prevalence of smoking observed in recent years in healthcare professionals but suggest the need to continue information, counselling and medical support campaigns aimed at achieving cessation of smoking.

Characteristics of patients with allergic polysensitization: the POLISMAIL study.

BACKGROUND: The natural history of respiratory allergy is commonly characterized by a worsening of symptom severity, frequent comorbidity of rhinitis and asthma, and polysensitization to aeroallergens. The polysensitization phenomenon starts since childhood and is rare to find monosensitized adult patients. However, there are few studies investigating the characteristics of polysensitized patients. METHODS: This study was performed on a large cohort of patients with allergic rhinitis (assessed by ARIA criteria) and/or mild to moderate asthma (assessed by GINA). The kind and the number of sensitizations, their patterns, and the relation with quality of life (QoL) measured by the Juniper's RQLQ guestionnaire, were evaluated. RESULTS: Globally 418 patients (50.2% males, 49.8% females, mean age 26.4 years, range 3.5-65 years, 64 smokers, 371 non-smokers) were enrolled: 220 had allergic rhinitis alone, and 198 allergic rhinitis and asthma. The mean number ofsensitizations was 2.6. Three hundred-five patients (73%) had persistent rhinitis (PER), 220 of them with moderate-severe form. There was no significant derence in rate of rhinitis and asthma in monosensitized or polysensitized patients. Most patients were sensitized to pollens, whereas only 24.2% of them were sensitized to perennial allergens. Polysensitization was significantly associated with some issues of QoL, confirming previous findings, but not with number ofsensitizations. CONCLUSIONS: This study provides data confirming for poly-sensitized patients the relevance of ARIA classification of AR. PER is the most common form of AR in this cohort, symptoms are frequently moderate-severe, and asthma is present in about the half of patients with AR.

Dose dependence of efficacy and safety of subcutaneous immunotherapy.

A number of experimental and clinical evidence has shown that exposure to high amounts of allergen molecules favours the development of tolerance. This is true also for subcutaneous immunotherapy (SCIT), for which a dose dependence of clinical efficacy was clearly demonstrated. The effective doses, measured as microg of major allergens, to be administered during maintenance treatment were established for the main allergens. Regarding pollens, the range of effectiveness corresponds to 25-41 and 13-20 microg of major allergens Phl p 5 and Phl p 6 for grasses, to 10-47 microg of Amb a 1 for ragweed, to 12 microg of Bet v 1 for birch, and to 6.2 microg of Par j 1 for Parietaria. With house dust mites, a maintenance dose of 5-11.5 microg of the major allergen from Dermatophagoides pteronyssinus Der p 1 is associated to clinically relevant effects, and with cat epithelium the clinical success is observed using a dose of 13-15 microg of Fel d 1. Nevertheless, there are adverse reactions facing SCIT, which are related to the amount of injected allergen. In fact, the safety decreases when the administered doses increase. This has led to "optimal doses" being defined which show a good balance between efficacy and safety (corresponding for example to a dose of 7 microg for Der p 1 and of 13 microg for Fel d 1). The dose dependency with respect to both efficacy and safety makes essential to accurately consider the risk/benefit ratio in each patient eligible for SCIT.

Anaphylaxis to honey in pollinosis to mugwort: a case report.

A case of anaphylaxis to honey in a 19 year old female sensitized to Compositae pollen is described. The patient suffered from summer rhinoconjunctivitis since seven years; in January 2006, ten minutes after eating bread and honey she developed angioedema of the lips and tongue, runny nose, cough, dyspnoea, and collapse, requiring hospitalization and treatment with high dose corticosteroids and anti-histamines. After two weeks, skin prick tests (SPT) with a standard panel of inhalant allergens and prick + prick with a number of kinds of honey were performed. SPTs were positive to mugwort, ragweed, dandelion, and goldenrod. Concerning honey, the prick + prick was positive to "Millefiori" (obtained from bees foraging on Compositae) and also to sunflower, limetree, and gum tree honey, while was negative for other kinds of honey, including the frequently used chestnut honey and acacia honey. The allergenic component responsible of anaphylaxis in this case seems to be a molecule occurring in Compositae pollens, as previously reported for other three reports, but also in pollen from plants of different families. Honey contains a large number of components derived from bees, such as gland secretions and wax, as well as from substances related to their foraging activity, such flower nectar and pollens (1, 2). Honey as a food has been associated to allergic reactions and particularly to anaphylaxis (3-6). Among the pollens, the role of Compositae is somewhat controversial, since its responsibility is clear in some studies (3, 5, 6) but considered negligible in others (7). Here we present the case of a patient sensitized to Compositae pollen who had an anaphylactic reaction to the ingestion of honey obtained from bees foraging on Compositae flowers and was tested with a number of different varieties of honey.

Different outcomes of pulmonary rehabilitation in patients with COPD with or without exacerbations.

BACKGROUND: Pulmonary rehabilitation is recognised as an effective treatment in reducing disability and improving the quality of life in patients with COPD. We evaluated the effects of a course of pulmonary rehabilitation in improving the physical performance and lung function in patients with or without COPD exacerbations. METHODS: 74 patients with COPD were enrolled, 37 (24 males and 13 females, mean age 74.6 years) without exacerbations (group A), and 37 (23 males, 14 females, mean age 73.9 years) with exacerbations (group B). The latter must have had the latest exacerbation at least one month before the inclusion. All patients underwent to a rehabilitation programme of 8 visits in 4 weeks in a day-hospital setting, with exercise training, respiratory muscle training and education on COPD. The changes in physical performance and lung function in respect to baseline were measured by a 6-minute walking test, using phethysmography, and by an analogic manometer measuring maximal inspiratory and expiratory pressures (MIP, MEP). RESULTS: Patients of group A showed a mean increase in timed walk distance of 58.38 +/- 57.46 m, compared to a mean increase of 31.38 +/- 44.78 m in group B patients (p = 0.028). As to lung function, a mean increase of 178.92 +/- 132.28 ml in FEV1 in group A versus 67.84 +/- 102.04 ml in group B (p < 0.0001) and a mean increase of 22.36 +/- 25.06 cm H2O in MEP in group A versus 7.70 +/- 12.28 cm H2O in group B (p = 0.002) was found. CONCLUSIONS: These findings indicate that patients with COPD with exacerbations achieve a less favourable outcome of pulmonary rehabilitation, with a significantly lower improvement of physical performance, respiratory muscle strength and lung function in respect to subjects without exacerbations.

Differential fluorescent staining method for detection of bacteria in blood cultures, cerebrospinal fluid and other clinical specimens.

The aim of this study was to evaluate a differential staining method to distinguish gram-positive from gram-negative bacteria in fluorescence. The method is based on two fluorochromes, one acting in the wavelength of red, i.e. the acridine orange, and another acting in the wavelength of green, i.e. the fluorescein. With this method, gram-positive bacteria appear yellow and gram-negative bacteria appear green. In view of the importance of a rapid aetiological diagnosis in cases of septicaemia, the differential staining method in fluorescence was compared with Gram stain for the detection of bacteria in blood. Of 5,820 blood cultures entered into the study and identified by the Bactec 9120 fluorescent series instrument (Becton Dickinson Europe, France), 774 were positive. Of the 774 positive cultures, 689 yielded only a single organism. The differential staining method in fluorescence detected 626 of the 689 cultures, while Gram stain detected 468. On the basis of these results, the sensitivity of the differential staining method in fluorescence was 90.9%, while that of Gram stain was 67.9%. The difference between the two methods was statistically significant ( P<0.001). The differential fluorescent staining method was more sensitive than Gram stain in the detection of bacteria in blood cultures during the incubation period. This technique provides a rapid, simple and highly sensitive staining method that can be used in conjunction with subculture methods. Whereas subculture requires an incubation period of 18-24 h, the fluorescent staining technique can detect bacteria on the same day that smears are prepared and examined. The differential fluorescent staining method was also evaluated for its ability to detect microorganisms in cerebrospinal fluid and other clinical specimens. The microorganisms were easily detected, even when bacterial counts in the specimens were low.