Chronic cough in adults: recommendations from an Italian intersociety consensus.

BACKGROUND: Chronic cough (CC) is a burdensome health problem in adult and older people, with a major impact on quality of life. Its management is often troublesome, and many guidelines have been released. Notwithstanding, a proportion of cases still do not reach a definite diagnosis and resolutive treatment. A coordinated approach between different specialists would be highly recommended, but its implementation in clinical practice suffers from the lack of shared protocols and poor awareness of the problem. The present consensus document has been implemented to address these issues. AIMS: To develop evidence-based recommendations for the management of adults with CC. METHODS: A 12-member expert task force of general practitioners, geriatricians, pneumologists, allergologists, otorhynolaringologists and gastroenterologists was established to develop evidence-based recommendations for the diagnostic and therapeutic approach to subjects with CC. A modified Delphi approach was used to achieve consensus, and the US Preventive Services Task Force system was used to rate the strength of recommendations and the quality of evidence. RESULTS: A total of 56 recommendations were proposed, covering 28 topics and concerning definitions and epidemiology, pathogenesis and etiology, diagnostic and therapeutic approach along with the consideration of specific care settings. CONCLUSION: These recommendations should ease the management of subjects with CC by coordinating the expertise of different specialists. By providing a convenient list of topics of interest, they might assist in identifying unmet needs and research priorities.

Adult Pulmonary Intensive and Intermediate Care Units: The Italian Thoracic Society (ITS-AIPO) Position Paper.

The imbalance between the prevalence of patients with acute respiratory failure (ARF) and acute-on-chronic respiratory failure and the number of intensive care unit (ICU) beds requires new solutions. The increasing use of non-invasive respiratory tools to support patients at earlier stages of ARF and the increased expertise of non-ICU clinicians in other types of supportive care have led to the development of adult pulmonary intensive care units (PICUs) and pulmonary intermediate care units (PIMCUs). As in other European countries, Italian PICUs and PIMCUs provide an intermediate level of care as the setting designed for managing ARF patients without severe non-pulmonary dysfunction. The PICUs and PIMCUs may also act as step-down units for weaning patients from prolonged mechanical ventilation and for discharging patients still requiring ventilatory support at home. These units may play an important role in the on-going coronavirus disease 2019 pandemic. This position paper promoted by the Italian Thoracic Society (ITS-AIPO) describes the models, facilities, staff, equipment, and operating methods of PICUs and PIMCUs.

How Do Storms Affect Asthma?

PURPOSE OF REVIEW: There are observations in various geographical areas that thunderstorms occurring during pollen seasons can induce severe asthma attacks in pollinosis patients. RECENT FINDINGS: An accredited hypothesis explaining the association between thunderstorms and asthma suggests that storms can concentrate pollen grains at ground level, which may then release allergenic particles of respirable size in the atmosphere after their imbibition of water and rupture by osmotic shock. During the first 20-30 min of a thunderstorm, patients affected by pollen allergy may inhale a high quantity of the allergenic material that is dispersed into the atmosphere as a bioaerosol of allergenic particles, which can induce asthmatic reactions, often severe. Subjects without asthma symptoms, but affected by seasonal rhinitis can also experience an asthma attack. A key message is that all subjects affected by pollen allergy should be alerted to the danger of being outdoors during a thunderstorm in the pollen season, as such events may be an important cause of severe asthma exacerbations. In light of these observations, it is useful to predict thunderstorms and thus minimize thunderstorm-related events. Patients with respiratory allergy induced by pollens and molds need to be informed about a correct therapeutic approach of bronchial asthma by inhalation, including the use of bronchodilators and inhaled corticosteroids. The purpose of this review is to focalize epidemiological, etiopathogenetic, and clinical aspects of thunderstorm-related asthma.

Persistence with inhaled corticosteroids reduces the risk of exacerbation among adults with asthma: A real-world investigation.

BACKGROUND AND OBJECTIVE: Real-world evidence suggests that persistence with inhaled corticosteroids (ICS), the mainstay of asthma drug therapy, is generally poor. The effect of persistence with ICS on the risk of asthma exacerbation was addressed in a population-based study. METHODS: The cohort of 2335 beneficiaries of the National Health Service provided by the Italian Region of Lombardy, aged 18-40 years and newly treated with ICS during 2005-2008, was followed from their first ICS dispensation until 2010. Discontinuation of treatment with ICS and starting oral corticosteroid therapy during follow-up were respectively regarded as proxies of poor persistence with asthma medication and asthma exacerbation (outcomes). A proportional hazards model was fitted to identify predictors of ICS discontinuation. Case-crossover and case-case-time-control designs and conditional logistic regressions were used to estimate the association between persistence with ICS and asthma exacerbation. RESULTS: Cumulative incidences of discontinuation were 36%, 57% and 78% at 6 months, 1 year and 5 years, respectively. Predictors of poor persistence were female gender, use of antibiotics during follow-up, absence of use of short-acting beta-agonists prior to and after starting treatment with ICS and starting and maintaining ICS monotherapy during follow-up. The odds ratios of asthma exacerbation (and 95% confidence intervals) associated with ICS exposure during the current period, contrasted with exposure during the reference period, were 0.4 (0.2, 0.9) and 0.3 (0.1, 1.0) from case-crossover and case-case-time-control estimates, respectively. CONCLUSION: Persistence with ICS treatment in adults with asthma reduces the risk of exacerbation in the real-life setting.

Incidence, Predictors, and Clinical Implications of Discontinuing Therapy with Inhaled Long-Acting Bronchodilators among Patients with Chronic Obstructive Pulmonary Disease.

Incidence, predictors and effect of discontinuation of long-acting bronchodilators on the risk of death or hospital admission among adults with Chronic Obstructive Pulmonary Disease (COPD) were assessed in a large population-based prospective study carried out by linking Italian healthcare utilization databases. Specifically, the cohort of 17,490 beneficiaries of the National Health Service in the Italian Region of Lombardy, aged 40 years or older, who started long-acting bronchodilators therapy during 2005-2008 was followed from first dispensation until 2012. During this period, patients who experienced discontinuation of long-acting bronchodilators were identified. Hospitalizations for COPD and deaths for any cause (composite clinical outcome) were also identified during follow-up. A Cox proportional hazards model was fitted to identify predictors of discontinuation. The case-crossover design was used to assess the implications of treatment discontinuation on the clinical outcome risk. Cumulative incidences of discontinuation were, respectively, 67%, 80%, and 92% at 6 months, 1 year, and 5 years since initial treatment. Significant predictors of discontinuation were female gender, younger age, starting treatment with fixed-dose combination of inhaled bronchodilators and corticosteroids, using antibiotics, inhaled long-acting bronchodilators and corticosteroids and not using short-acting bronchodilators, other respiratory drugs and systemic corticosteroids during follow-up. Odds ratios (95% confidence intervals) for the clinical outcome associated with not discontinuing long-acting bronchodilators was 0.64 (0.50 to 0.82). In conclusion, in the real-life setting, discontinuation of inhaled long-acting bronchodilators in adults with COPD is high even after just 6 months, even though persistence to these drugs reduces the risk of severe outcomes.

Ragweed pollen concentration predicts seasonal rhino-conjunctivitis and asthma severity in patients allergic to ragweed.

In this work, we investigate the correlation between ragweed pollen concentration and conjunctival, nasal, and asthma symptom severity in patients allergic to ragweed pollen using ambient pollen exposure in the Milan area during the 2014 ragweed season We calculate the pollen/symptom thresholds and we assess the effectiveness of ragweed allergen immunotherapy (AIT). A total of 66 participants allergic to ragweed (Amb a 1) were enrolled in the study and divided into two groups: AIT treated (24) and no AIT treated (42). Pollen counts and daily symptom/medication patient diaries were kept. Autoregressive distributed lag models were used to develop predictive models of daily symptoms and evaluate the short-term effects of temporal variations in pollen concentration on the onset of symptoms. We found significant correlations between ragweed pollen load and the intensity of symptoms for all three symptom categories, both in no AIT treated (τ = 0.341, 0.352, and 0.721; and ρ = 0.48, 0.432, and 0.881; p-value < 0.001) and in AIT treated patients ([Formula: see text]= 0.46, 0.610, and 0.66; and ρ = 0.692, 0.805, and 0.824; p-value < 0.001). In both groups, we observed a positive correlation between the number of symptoms reported and drug use. Mean symptom levels were significantly higher in no AIT treated than in AIT treated patients (p-value < 0.001) for all symptom categories. Pollen concentration thresholds for the four symptom severity levels (low, medium-low, medium-high and high) were calculated. Ragweed pollen concentration is predictive of symptom severity in patients with a ragweed (Amb a 1) allergy. Patients treated with AIT had significantly reduced mean symptom levels compared to those without AIT.

Multisocieties position paper: Microbiological surveillance on flexible endoscopes.

Transmission with endoscopes, particularly duodenoscope, of potential lethal infections prompted different scientific societies to deliver recommendations aimed reducing this risk. Some International societies extended recommendations on microbial surveillance to all the endoscopes and devices used in the reprocessing procedure. Considering the relevance of the topic, 8 Italian scientific societies of physicians, nurses and technical operators prepared a concerted document taking into account Institutional advisories and facilities in Italy. The rules for a correct microbial surveillance on endoscopes were detailed in term of what, how and when to perform the procedure, also suggesting behaviors in case of contamination.

ARIA-ITALY multidisciplinary consensus on nasal polyposis and biological treatments.

In the recent years, it was recognized that type-2 inflammation links many forms of nasal polyposis with severe asthma. Thus, some biological drugs developed for severe asthma appeared to exert an effect on nasal polyposis. So far, there are several trials supporting this concept; therefore, some monoclonal antibodies for severe asthma were assessed also in polyposis, with promising results. Since different specialists are involved in the management of nasal polyposis (eg, pulmonologists, ENT, allergists), it was felt that an educational and informative document was needed to better identify the indications of biologicals in nasal polyposis. We collected the main Italian Scientific Societies, and prepared (under the Allergic Rhinitis and its Impact on Asthma, ARIA) a document endorsed by all Societies, to provide a provisional statement for the future use of monoclonal antibodies as a medical treatment for polyposis. It is the first nationwide endorsed document on this aspect. The current pathogenic knowledge and the experimental evidence are herein reviewed, and some suggestions for a correct prescription and follow-up are provided.

Effects of biological therapies on chronic rhinosinusitis in severe asthmatic patients.

OBJECTIVE: The introduction of monoclonal antibody (mAb) therapies represents a promising treatment for refractory chronic rhinosinusitis (CRS). We assessed the effects of selected mAbs (omalizumab, mepolizumab, benralizumab) on CRS in severe asthmatic patients in a real-life setting. METHODS: A prospective observational study on severe asthmatic patients, treated with 3 different mAb (omalizumab, mepolizumab, benralizumab), and comorbid CRS was conducted. All patients were followed for 52 weeks. The degree of nasal control, SinoNasal Outcome Test (SNOT) 22, Nasal Polyp Score (NPS), Lund Kennedy Score (LKS) were collected at baseline and at 52-week. RESULTS: 40 patients (33 with nasal polyps) were studied. 33 patients (82.5%) had uncontrolled nasal disease at baseline, and 15 (37.5%) were uncontrolled after 52 weeks. Significant improvement was observed for SNOT 22 (P < 0.001), SNOT 1-12 (P < 0.001) and degree of nasal control (P < 0.001). Differences in NPS (P = 0.130) and LKS (P = 0.124) were not significant. Net change in the above-mentioned parameters among the three treatment groups was not significantly different. CONCLUSIONS: The study shows an improvement of nasal symptoms after 52 weeks of mAb treatment, which was not associated with significant improvement of endoscopic findings. Larger studies are needed to assess the real-life efficacy of mAbs in CRS.

Mepolizumab as the first targeted treatment for eosinophilic granulomatosis with polyangiitis: a review of current evidence and potential place in therapy.

Mepolizumab is an anti-interleukin-5 (IL-5) humanized monoclonal antibody that binds to free IL-5. It induces bone marrow eosinophil maturation arrest and decreases eosinophil progenitors and subsequent maturation in the blood and bronchial mucosa. Its use has been extensively studied in severe eosinophilic asthma at a dose of 100 mg subcutaneously (SC) every 4 weeks and, more recently, in other hypereosinophilic syndromes. Eosinophilic granulomatosis with polyangiitis (EGPA) is an eosinophilic vasculitis that may involve multiple organs. Characteristic clinical manifestations are asthma, sinusitis, transient pulmonary infiltrates and neuropathy. Among the numerous pathways involved in the pathogenesis of EGPA, the Th-2 phenotype has a main role, as suggested by the prominence of the asthmatic component, in triggering the release of key cytokines for the activation, maturation and survival of eosinophils. In particular, IL-5 is highly increased in active EGPA and its inhibition can represent a potential therapeutic target. In this scenario, mepolizumab may play a therapeutic role. After some positive preliminary observations on the use of mepolizumab in small case series of EGPA patients with refractory or relapsing disease despite standard of care treatment, a randomized controlled trial was published in 2017. Mepolizumab at a dose of 300 mg administered by SC injection every 4 weeks proved effective in prolonging the period of remission of the disease, allowing for reduced steroid use. The positive results of this study, which met both of the primary endpoints, led to the approval in the USA of mepolizumab in adult patients with EGPA by the Food and Drug Administration in 2017. Therefore, mepolizumab can be officially considered as an add-on therapy with steroid-sparing effect in cases of relapsing or refractory EGPA. However, the most appropriate dose and duration of therapy still need to be determined. Future studies on larger multinational populations with prolonged follow-up are warranted.

Long-term macrolides in diffuse interstitial lung diseases.

In the present review we provide currently available evidence for the use of macrolides in the treatment of diffuse interstitial lung diseases (ILDs). Up to now, research on macrolides has mainly focused on three areas. First, macrolides have shown some promising results in cellular models and case reports as antifibrotic agents, by promoting autophagy and clearance of intracellular protein aggregates and acting as regulators of surfactant homeostasis. Secondly, macrolides have an immunomodulatory effect, which has been applied in some organising pneumonia cases. In particular, macrolides have been tested in association with systemic corticosteroids as steroid-sparing agents and alone as either first-line agents in mild cases or second-line agents where steroids were poorly tolerated or had failed. Thirdly, a recent area of research concerns the possible role of macrolides as modulators of lung microbiota and the host-microbiota interaction. This function has been particularly studied in idiopathic pulmonary fibrosis patients, in whom changes in microbiota have been proved to be associated with disease progression. However, the lack of high-quality studies makes the application of macrolide therapy in ILDs a field in which research should be conducted on a large scale.

Prescription bias and factors associated with improper use of inhalers.

Many different inhalers are available for delivering aerosol therapy in respiratory medicine. As a consequence, the prescribing physicians may have some difficulty tailoring the most suitable inhaler to each patient. This multicenter, observational study using a self-administered questionnaire analyzed the characteristics of a large sample of patients (n = 1,305; 55% females; mean age 57.4, with a range of 15-88 years; most suffering from asthma or chronic obstructive pulmonary disease [COPD]) familiar with several different types of inhalers in relation to their most commonly used delivery device. Data on the inhalation technique for 2,057 observations of 1,126 patients using device-specific checklists and factors associated to misuse were also evaluated. Prevalent usage of newer dry powder inhalers (DPIs) was significantly associated with male sex, higher education, better respiratory function, and prescription from a respiratory physician. Patients using DPIs had received less instruction by health caregivers and were more likely to have read the instruction leaflet than users of metered dose inhalers (MDIs). Under these conditions, inhaler misuse was common and similar for both pressurized metered dose inhalers (pMDIs) and DPIs. For both types of inhalers, misuse was significantly and equally associated to increased age, less education, and less instruction by health care personnel. We conclude that many doctors are not familiar with the relevant characteristics of currently available inhalers. The prescription of newer DPIs may be subjected to gender, socio-economic, and instruction bias. The simple change of device from the pMDI to the newer DPIs is not associated with improved inhalation technique.

[Hypersensitivity pneumonitis in budgerigar fanciers. A seldom recognised disease?]. / Polmonite da ipersensibilità nei possessori di pappagallini.

A hypersensitivity pneumonitis (HP) can be easily recognized either in acute manifestations, as in farmer lung syndrome, and in subacute, as bird fancier's lung; the following case shows an insidious HP occurred to a 44 year old, non smoker woman, fancier--during the winter--of 8 budgerigars kept in the kitchen. The authors suppose HP is underestimated, considering Italy's likely high number of bird fanciers, versus only 260 general cases of HP that have been reported every year in Italy (1999-2002).

Multiple primary synchronous malignant tumors.

BACKGROUND: Patients with primary multiple malignancies are progressively increasing due to prolonged survival of cancer patients and to the advances in diagnostic techniques and therapeutic options. CASE PRESENTATION: Here we present a 66 year-old caucasian patient with four synchronous primary malignant tumors affecting the lung, oropharynx, large bowel and prostate gland, respectively, treated with multidisciplinary approach. CONCLUSIONS: The increased incidence of multiple malignant tumors is a real challenge to the clinician and clinical attention should be made to avoid a misdiagnosis. In addition an early diagnosis is essential to achieve a radical treatment. We believe that the treatment modality should be carefully made and tailored on the individual patient suffering from this disease.

[Hematoma of the rectus muscle of abdomen in a patient treated with nadroparin]. / Ematoma del muscolo retto addominale in corso di trattamento con nadroparina.

The case of large rectus abdominis hematoma of a patient affected by chronic obstructive polmunary disease, complicated by respiratory insufficiency, treated with low molecolar weight heparin (LMWH) is described; a spontaneous rectus hematoma is an uncommon condition that is to be considered in patient treated with LMWH at prophylactic dose, even in absence of other predisposing conditions, in the case of acute abdominal pain with evidence of abdominal mass and anemic syndrome.

Endovascular treatment of a ruptured pulmonary artery aneurysm in a patient with Behçet's disease using the Amplatzer Vascular Plug 4.

A pulmonary artery aneurysm is a common manifestation and the leading cause of mortality in Behçet's disease. We describe a case of spontaneous rupture of a pulmonary artery aneurysm that, due to the inadequacy of medical therapy and the disadvantages of surgery, became the ideal candidate for endovascular management and was successfully performed by using the Amplatzer Vascular Plug 4.

Inhaler mishandling is very common in patients with chronic airflow obstruction and long-term home nebuliser use.

Inhalers and nebulisers are devices used for delivering aerosolised drugs in subjects with Chronic Airflow Obstruction (CAO). This multicentre, cross-sectional observational study was performed in a large population of outpatients with CAO regularly using home aerosol therapy and referring to chest clinics. The aims of the study were to compare the characteristics of the group of subjects with CAO who were using home nebulisers but also experienced with inhalers vs. those only using inhalers and to investigate whether the first group of subjects was particularly prone to inhaler misuse. Information was gained evaluating the responses to a standardised questionnaire on home aerosol therapy and the observations of inhaler technique. We enrolled 1527 patients (58% males; mean ± SE; aged 61.1 ± 0.4 years; FEV1% pred 69.9 ± 0.6; 51% and 44% respectively suffering from COPD and asthma) who were only inhaler users (OIU group) and 137 (85% males; aged 67.7 ± 1.3 years; FEV1% pred 62.3 ± 2.9; 60% and 23% respectively suffering from COPD and asthma) who were using both nebulisers and inhalers (NIU group). Nebuliser users were older, had more severe obstruction, related symptoms and health care resources utilisation. Nebulisers users performed more critical inhalers errors than those of the OIU group (49% vs. 36%; p = 0.009). We conclude that our patients with CAO and regular nebuliser treatment had advanced age, severe respiratory conditions and common inhaler misuse.