Prevention of recurrent respiratory tract infections: a literature review of the activity of the bacterial lysate Lantigen B.

OBJECTIVE: Lantigen B, a bacterial lysate, was developed in the 1960s and showed a prophylactic effect in patients with recurrent respiratory tract infections. The objective of this article is to review the literature to update the efficacy and safety profile of Lantigen B in preventing recurrent respiratory tract infections (RRTI). MATERIALS AND METHODS: Articles available from international data banks and producing company archives were used. Only clinical studies providing a control group were considered. The effects of Lantigen B on the number of infectious episodes or comparable parameters were analyzed. RESULTS: 22 randomized clinical trials on 4,571 patients published between 1963 and 2014, with different methodologic accuracy, consistently demonstrated that Lantigen B reduced RRTI vs. placebo (RR -0.47; 95% CI = -0.38 to -0.56). The RR always favored Lantigen B in all the other subsets analyzed in adults with RRTI (RR = -0.48; 95% CI = - 0.33 to -0.62) and children (RR = -0.490; 95% CI = - 0.36 to -0.61). Unfortunately, some studies performed in the past evaluated a small number of patients, and clinical procedures were not always performed according to the more recent good clinical practices. Despite these evident limitations of considered studies, the response frequency has remained almost unchanged since the first articles in the 1960s. CONCLUSIONS: These data confirm the efficacy of Lantigen B alone in the prophylaxis of acute respiratory infections in adults and children but also suggest that Lantigen B, used with novel therapeutic strategies, can further improve clinical outcomes.

The prevalence of sleep impairments and predictors of sleep quality among patients with asthma.

BACKGROUND: Sleep is a significant dimension of daily life. However, only a few studies have examined the sleep quality of asthmatics in a real-world clinical settings. OBJECTIVE: This study is aimed to estimate the prevalence of sleep impairments among asthmatic patients and examine the relationship between sleep quality, asthma control, rhinitis symptoms, and sociodemographic characteristics. METHODS: The present study adopted the observational cross-sectional research design that has been designed by the Italian Respiratory Society and used valid assessments to measure the study variables. RESULTS: Data from 1150 asthmatic patients (mean age 51.01 years ± 16.03) were subjected to analysis. 58.3% of the patients had impaired sleep quality (Pittsburgh Sleep Quality Index [PSQI] total scores > 5), and their mean PSQI score was 5.68 (SD = 3.4). A significant correlation emerged between sleep quality and asthma control (p = 0.0001) and a significant albeit weak correlation emerged between PSQI total scores and Total 5 Symptoms Score (r = 0.24, p = 0.0001). Sleep quality was significantly associated health-related quality of life [HRQoL]. (r = 0.50, p < 0.001). After exclusion of patients at risk for Obstructive Sleep Apnea Syndrome (OSAS) and Gastro Esophageal Reflux Disease (GERD), the most important determinants of PSQI score were HRQoL, In the entire sample asthma control is the strongest predictor of both sleep quality and HRQoL. CONCLUSIONS: The results of this real-world study highlight the prevalence, impact and predictors of sleep disturbances in asthmatic patients and suggest the need for physicians to detect poor sleep quality.

What drives inhaler prescription for asthma patients? Results from a real-life retrospective analysis.

BACKGROUND: The choice of inhaler device for asthma patients depends upon multiple attributes. We investigated factors that may drive general practitioners (GPs) and respiratory specialists in the prescription of inhaler devices for asthma patients who initiated inhalation therapy. METHODS: We retrospectively analysed prescriptions by GPs and respiratory specialists to asthma patients commencing inhaled corticosteroid/long-acting ß2-agonist combination therapy available as both pressurised metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs). Patient characteristics were compared by device and multivariate analysis was used to model the likelihood of receiving a pMDI as opposed to a DPI in order to identify drivers for prescription. A sample of the respiratory specialists completed an ad-hoc survey of their perceived success in achieving asthma control in their patients and barriers to attaining full control. RESULTS: Prescription of a particular inhaler device was unrelated to the characteristics of the patients. Multivariate analysis revealed that the main driver for the choice of inhaler device was the medication (Odds Ratio and 95% Confidence Interval, respectively for GPs and specialists: 0.19 [0.16-0.23]; 0.17 [0.08-0.37]). Specialists perceived asthma as being inadequately controlled in 41% of their patients, and considered patients' difficulties in using DPIs and pMDIs as instrumental in this, citing a need for a novel, more effective inhaler technology. CONCLUSION: Physicians choose inhaler devices according to the prescribed drugs and not to the characteristics of the individual patient. This may reflect a lack of confidence in existing inhaler devices and underlines the need for technologies, which are more reliable and easier to use by patients.

The Portuguese version of Rhinitis and Asthma Patient's Perspective (RAPP): Validation and assessment.

BACKGROUND: Allergic rhinitis (AR) and asthma are two common chronic diseases that often coexist. There is a need for a validated tool to evaluate HRQoL of Portuguese speakers with asthma and/or rhinitis patients in clinical practice. OBJECTIVES: To adapt and validate RhinAsthma Patient Perspective (RAPP) in Portuguese. METHODS: The RAPP questionnaire was translated into Portuguese. Asthmatics with comorbidities and rhinitis attending the allergy department of Coimbra University Hospital were asked to complete the Portuguese translation of RAPP, in addition to the SF-12, ACT, and a Symptomatologic VAS twice, with a 4-week interval between visits. During Visit 2, a Global Rating Scale (GRS) was completed to assess any change in health status. Scale dimensions, internal consistency and convergent validity, reliability, discriminant ability and responsiveness to change, as well as Minimal Clinical Difference were assessed. RESULTS: Factor and confirmatory analysis confirm the unidimensional structure of the questionnaire. Internal consistency has been shown to be satisfactory (0.82 visit 1 and 0.86 at visit 2). The tool is able to discriminate between patients on the basis of asthma severity, asthma control level, and rhinitis severity; convergent validity showed a significant correlation with SF-2 Physical component (r=-0.46 and 0.42, p at Visits 1 and 2). An ICC of 0.97 and a CCC=0.94 indicate that the tool is highly reliable. Responsiveness was shown in detecting a significant association with GRS changes (r=0.41, p<0.01) and ACT (r=-0.47, p<0.01) but not with VAS. (r=.14, n.s.). MID value was 2 points. CONCLUSIONS: The Portuguese version of RAPP has been demonstrated to have good measurement properties and sensitivity to health changes, which will provide a valid, reliable and standardized HRQoL measurement in patients with asthma and comorbid allergic rhinitis in clinical practice.

Cross-cultural adaptation and validation of the RhinAsthma Patient Perspective (RAPP) in Spanish.

OBJECTIVE: the RhinAsthma Patient Perspective (RAPP) is the only available tool to assess HRQoL in daily practice. The aim of this study is to cross-culturally validate the RAPP in Spanish. METHODS: The RAPP was translated into Spanish. Adult patients receiving usual care for asthma and allergic rhinitis (AR) were recruited consecutively and assessed twice with a four-week interval between visits to test the psychometric properties of the questionnaire. RESULTS: 149 patients (62.8% female) with a mean age of 37.7 years completed the study. Exploratory and confirmatory factor analysis confirmed the uni-dimensional structure of the questionnaire. Internal consistency (0.73 at visit 1; 0.87 at visit 2), convergent and discriminant validity (p<.05 at both visits) were satisfactory. Reliability was confirmed by an ICC of 0.69 and a CCC of 0.74. Responsiveness was supported by a significant association with VAS (r=0.28, p<0.003) and ACT (r=-0.35, p<0.01). The minimal clinical difference (MID) value in the analyzed population was 2. CONCLUSIONS: The Spanish version of RAPP was demonstrated to have satisfactory psychometric properties and is a valid, reliable and responsive tool for the assessment of asthma and AR HRQoL in clinical practice.

Transoral glossoepiglottopexy in the treatment of adult obstructive sleep apnoea: a surgical approach.

SUMMARY: The treatment of obstructive sleep apnoea syndrome (OSAS) is still a matter of debate; among the different therapeutic alternatives, both surgical and conservative, treatment with continuous positive airway pressure (CPAP) is considered the "gold standard". The recent scientific literature reports that even if CPAP represents an effective solution for sleep apnoeas, 12% of patients do not benefit from its use. In most cases, primary collapse of the epiglottis is responsible for failure. We developed a surgical technique that provides a stable support to the epiglottis without influencing its function during swallowing while preserving laryngeal anatomy and physiology. The procedure we propose is based on that conceived by Monnier for children affected by laryngomalacia. We analysed a group of 20 patients who underwent glossoepiglottopexy between January 2015 and September 2016 and compared data (AHI, ODI, t90, ESS, EAT10, etc.) collected before and 6 months after surgery to demonstrate the safety and effectiveness of our glossoepiglottopexy (GEP). The results allow us to consider GEP as a valid choice to treat adults who suffer from sleep apnoeas.

Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease: an Interasma (Global Asthma Association - GAA) and World Allergy Organization (WAO) document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA) and Global Allergy and Asthma European Network (GA2LEN).

Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 µm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect the physician's considerations of disease features, phenotype, and response to previous therapy. This article is being co-published in Asthma Research and Practice and the World Allergy Organization Journal.

Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease: an Interasma (Global Asthma Association - GAA) and World Allergy Organization (WAO) document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA) and Global Allergy and Asthma European Network (GA2LEN).

Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 µm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect the physician's considerations of disease features, phenotype, and response to previous therapy. This article is being co-published in Asthma Research and Practice and the World Allergy Organization Journal.

Anxiety and depression in cystic fibrosis.

Cystic fibrosis (CF) is the most common genetic disorders in the Caucasian population, with estimated between 70,000 and 100,000 patients worldwide. Even if improved diagnostics and clinical management have led to an increased life expectancy, CF still remains a disease that significantly impacts patients' life in terms of symptoms, daily functioning, psychological morbidity and health related quality of life. Available data suggest that symptoms of anxiety and depression, such as in other chronic conditions, are common features in CF patients and in their caregivers, with a significant impact on disease outcomes. In this review we analyze and discuss the findings of The International Depression and Anxiety Epidemiological Study (TIDES), recently published on Thorax. This study was aimed to determine the prevalence of symptoms of depression and anxiety in a large population of adolescents and adults with CF and in parents of children with CF, across eight European countries and the USA. The TIDES provides useful insights about the psychological/psychiatric comorbidities in CF and its conclusions are absolutely shareable. Nevertheless some doubts remain on the methods and the tools. Further investigation and understanding of anxiety and depression in CF (in terms of prevalence, association with clinical, psychological and sociocultural factors) is necessary and evidence is crescent that a global and multidisciplinary approach is wanted.

Why use long acting bronchodilators in chronic obstructive lung diseases? An extensive review on formoterol and salmeterol.

Long-acting ß2-adrenoceptor agonists, formoterol and salmeterol, represent a milestone in the treatments of chronic obstructive lung diseases. Although no specific indications concerning the choice of one molecule rather than another are provided by asthma and COPD guidelines, they present different pharmacological properties resulting in distinct clinical employment possibilities. In particular, salmeterol has a low intrinsic efficacy working as a partial receptor agonist, while formoterol is a full agonist with high intrinsic efficacy. From a clinical perspective, in the presence of low ß2-adrenoceptors availability, like in inflamed airways, a full agonist can maintain its bronchodilatory and non-smooth muscle activities while a partial agonist may be less effective. Furthermore, formoterol presents a faster onset of action than salmeterol. This phenomenon, combined with the molecule safety profile, leads to a prompt amelioration of the symptoms, and allows using this drug in asthma as an "as needed" treatment in patients already on regular treatment. The fast onset of action and the full agonism of formoterol need to be considered in order to select the best pharmacological treatment of asthma and COPD.

Quality-of-life issues in survivors to anaphylactic reactions to drugs.

The aim of this cross-sectional observational study was to explore quality of life and well-being in patients with drug-induced anaphylaxis. Two validated tools were used: the Drug Hypersensitivity Quality-of-Life Questionnaire (DrHy-Q) and the Psychological General Well-Being Index (PGWBI). Sixty-five patients (13 males) underwent data analysis. The mean DrHy-Q score was 62.82 ± 12.1. Mean PGWBI score was 64.03 ± 17.66. DrHy-Q score was significantly correlated with PGWBI total score (r = -0.314; P = 0.011) and with the following domains: Anxiety (r = -0.260; P = 0.036), Depressed mood (r = -0.406; P = 0.001), Positive well-being (r = -0.251; P = 0.004), and General Health (r = -0.352; P = 0.004). Compared with the Italian reference population, patients had a significantly reduced PGWBI total and domain score. Our results highlight for the first time how impaired HRQoL and distress commonly feature in survivors to anaphylactic reactions to drug.

Anxiety and depression in cystic fibrosis.

Cystic fibrosis (CF) is the most common genetic disorders in the Caucasian population, with estimated between 70,000 and 100,000 patients worldwide. Even if improved diagnostics and clinical management have led to an increased life expectancy, CF still remains a disease that significantly impacts patients' life in terms of symptoms, daily functioning, psychological morbidity and health related quality of life. Available data suggest that symptoms of anxiety and depression, such as in other chronic conditions, are common features in CF patients and in their caregivers, with a significant impact on disease outcomes. In this review we analyze and discuss the findings of The International Depression and Anxiety Epidemiological Study (TIDES), recently published on Thorax. This study was aimed to determine the prevalence of symptoms of depression and anxiety in a large population of adolescents and adults with CF and in parents of children with CF, across eight European countries and the USA. The TIDES provides useful insights about the psychological/psychiatric comorbidities in CF and its conclusions are absolutely shareable. Nevertheless some doubts remain on the methods and the tools. Further investigation and understanding of anxiety and depression in CF (in terms of prevalence, association with clinical, psychological and socio-cultural factors) is necessary and evidence is crescent that a global and multidisciplinary approach is wanted.

Differences in the efficacy and safety among inhaled corticosteroids (ICS)/long-acting beta2-agonists (LABA) combinations in the treatment of chronic obstructive pulmonary disease (COPD): Role of ICS.

Inhaled corticosteroids (ICS) are frequently recommended for the treatment of asthma and COPD, often in combination with long-acting beta2-agonists (LABA), depending on the severity of the disease and/or on the specific phenotype. Several ICS/LABA combinations are currently available that differ in their pharmacokinetic characteristics and dose of both components. Thus, this review assesses differences in the efficacy and the safety profiles of the ICS components in the two more frequently used ICS/LABA combinations (budesonide/formoterol and fluticasone/salmeterol) for the management of COPD. Whereas the basic mechanism of action is similar for all ICS (binding with the intracellular glucocorticoid receptor, which mediates both genomic and non genomic effects), the pharmacokinetic and characteristics of ICS are quite different in terms of receptor affinity, bioavailability, lipophilicity and drug persistence in the airways. Fluticasone persists longer in airway mucus and requires more time to dissolve in the lining fluid and then enter the airway wall, whereas budesonide is cleared more quickly from the airways. Comparative efficacy of the two major ICS/LABA combinations recommended for the treatment of COPD show similar efficacy in terms of reduction of exacerbations, improvement in forced expiratory volume in the first second (FEV1) and quality of life. One retrospective cohort study suggested a greater efficacy for the budesonide/formoterol combination on hospital or emergency department admissions, oral corticosteroid courses, and addition of tiotropium, and an observational real-life study reported a greater reduction of COPD exacerbations with budesonide/formoterol than with fluticasom/salmeterol combination. Among the potential side effects of chronic ICS treatment in patients with COPD, recently the use of fluticasone or fluticasone/salmeterol combination has been associated with a higher prevalence of pneumonia in the major long-term studies. On the other hand, no similar increased risk of pneumonia has been reported in patients with COPD treated with the budesonide/formoterol combination. A recent population-based cohort study from the Quebec database showed that the adjusted odds ratio for having severe pneumonia was higher for fluticasone (2.1) than for budesonide (1.17) or other ICS (1.41). Of the ICS studied, only fluticasone demonstrated a dose-related increase in risk of pneumonia in patients with COPD. This difference between fluticasone and budesonide may be explained by the longer retention of fluticasone in the airways, with potentially greater inhibition of type-1 innate immunity. Therefore, the risk:benefit ratio should be evaluated thoroughly when choosing an ICS/LABA combination for patients with COPD.

Asthma management among different specialists: results from a national Italian survey.

In Europe more than 50% of asthmatic treated patients have a not well-controlled asthma. The present survey aims at investigating how different specialists approach asthmatic patients. A web anonymous questionnaire was randomly administered to 604 General Practitioners (GPs), 241 Pneumologists and 131 Allergists. It concerned: epidemiology, diagnostic workup, follow-up and risk factors, treatment and future risk. A general agreement emerges about asthma diagnostic work-up. All categories are aware of the impact of comorbidities on asthma. LABA/inhaled steroids combination is considered the first choice treatment. Surprisingly, depot steroids and long-acting beta2 agonists (LABA) alone are still prescribed by GPs. Concerning monitoring tools, Allergists rely on inflammation biomarkers, whereas reduction of rescue medication is more relevant for GPs. Asthma Control Test (ACT) is considered time consuming by more than 50% of all physicians and is not known by most of GPs. Adherence is considered a crucial problem in asthma management. All categories seem to have a good knowledge about asthma. The cultural background may account for mild differences in asthma control tools and treatment options. GPs have a pivotal role in discriminating patients who need specific assessment by specialists. It is thus important that GPs and specialists share common tools for recognizing and managing those patients.

Illness perception, mood and coping strategies in allergic rhinitis: are there differences among ARIA classes of severity?

BACKGROUND: This study was designed to assess if illness perception, mood state and coping strategies differ according to allergic rhinitis (AR) persistence and severity. METHODS: Illness perception, mood profiles, coping behaviors and rhinitis symptoms were assessed by means of validated tools inpatients classified according to the Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines. RESULTS: Two hundred and thirty-one patients underwent data analysis. No difference in age, sex, socio-economic status, smoking habits was detected comparing patients according to AR severity, duration or 4 ARIA classes. Patients with intermittent AR reported higher scores than those with persistent AR in confusion-bewilderment of Profile of Mood States (POMS); patients with moderate/severe rhinitis had significantly higher scores than those with mild rhinitis in TSSS, Identity and Consequences. No differences were detected in all assessed outcomes in the 4 ARIA classes. CONCLUSIONS: The patient's perspective about AR is independent of persistence and severity of symptoms. This may explain why AR remains under-diagnosed and under-treated, even in its most severe forms. Self-management plans should consider the patient's perspective.

The role of cefditoren in the treatment of lower community-acquired respiratory tract infections (LRTIs): from bacterial eradication to reduced lung inflammation and epithelial damage.

OBJECTIVES: Lower respiratory tract infections (LRTIs), including pneumonia and acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD), are among the most common diagnoses in both outpatient and inpatient settings. Due to the burden of LRTIs healthcare providers must adopt practices focused on improving outcomes with the aim to reduce treatment failure and antibiotic resistances. Moreover, the role of acute and chronic infection in the pathogenesis of COPD has received considerable attention, since chronic infection can contribute to airways inflammation and COPD progression. This review discusses the role of cefditoren for the treatment of LRTIs, compared with the definition of "appropriate" of the WHO as "the cost-effective use of antimicrobials which maximizes clinical therapeutic effect while minimizing both drug-related toxicity and the development of antimicrobial resistance". RESULTS AND CONCLUSIONS: Cefditoren appears to meet the definition of "appropriate" for the treatment of LRTIs. In fact, this molecule shows an adequate pharmacokinetic profile without the need for any adjustment also in aged patients with mild renal impairment or mild-to-moderate hepatic dysfunction. The low drug-drug interaction potential of cefditoren can be an advantage also in poly-treated patients. The antimicrobial spectrum of cefditoren includes both Gram+ and Gram- bacteria, with high activity against Streptococcus pneumoniae, including drug-resistant strains, Haemophilus infuenzae and Moraxella chatarrhalis. Last, recent findings suggested that cefditoren can be a valid alternative to levofloxacin in outpatients with acute exacerbation of COPD; in this setting a treatment with cefditoren showed to be associated with a significant reduction of some key inflammatory markers involved in epithelial damage, including KL-6 and IL-6.

Randomized Controlled Trials and real life studies. Approaches and methodologies: a clinical point of view.

Randomized Controlled Trials (RCTs) are the "gold standard" for evaluating treatment outcomes providing information on treatments "efficacy". They are designed to test a therapeutic hypothesis under optimal setting in the absence of confounding factors. For this reason they have high internal validity. The strict and controlled conditions in which they are conducted, leads to low generalizability because they are performed in conditions very different from real life usual care. Conversely, real life studies inform on the "effectiveness" of a treatment, that is, the measure of the extent to which an intervention does what is intended to do in routine circumstances. At variance to RCTs, real life trials have high generalizability, but low internal validity. Recently the number of real life studies has been rapidly growing in different areas of respiratory medicine, particularly in asthma and COPD. The role of such studies is becoming a hot topic in respiratory medicine, attracting research interest and debate. In the first part of this review we discuss some of the advantages and disadvantages of different types of RCTs and analyze the strengths and weaknesses of real life trials, considering the recent examples of some studies conducted in COPD. We then discuss methodological approaches and options to overcome some of the limitations of real life studies. Comparing the conclusions of effectiveness and efficacy trials can provide important pieces of information. Indeed, these approaches can result complementary, and they can guide the interpretation of each other results.