Manuela Latorre

Sputum eosinophilia is a determinant of FEV1 decline in occupational asthma: results of an observational study

Objective To evaluate the potential determinants of forced expiratory volume in 1 s (FEV1) decline in workers with occupational asthma (OA) still exposed to the causative agent. We hypothesised that sputum eosinophilia might be a predictor of poor asthma outcome after diagnosis. Setting, design and participants In a specialistic clinical centre of the University Hospital of Pisa, we studied 39 participants (28 M, 11 F) diagnosed as having OA, routinely followed up between 1990 and 2009. They were a subgroup of 94 participants diagnosed as affected by OA in that period: 9 had been removed from work at the diagnosis, 21 were excluded for having ceased occupational exposure after few months from diagnosis, and 25 were lost at the follow-up or had no acceptable sputum measurements at the diagnosis. Estimates of the decline in FEV1 were obtained by means of simple regression analysis during the period of occupational exposure after diagnosis. Logistic regression was used to analyse the effects of factors (baseline FEV1 and sputum inflammatory cells, duration and type of exposure) that may potentially influence FEV1 decline. Results At follow-up (5.7+3.7 years), most participants were still symptomatic despite inhaled corticosteroids (ICS) treatment and had their occupational exposure reduced. Participants with higher sputum eosinophils (>3%) at baseline had a significantly greater decline of FEV1 (–52.5 vs −18.6 mL/year, p=0.012). Logistic regression showed that persistent exposure and sputum eosinophilia were significantly associated with a greater decline in FEV1 (OR 11.5, 95% CI 1.8 to 71.4, p=0.009 and OR 6.7, 95% CI 1.1 to 41.7, p= 0.042, respectively). Conclusions Sputum eosinophilia at diagnosis, together with the persistence of occupational exposure during follow-up, may contribute to a greater decline in FEV1 in patients with OA still at work. Further long-term studies are required as to whether intensive ICS treatment may be beneficial for patients with OA and increase ad eosinophilic inflammation.

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.

Neutrophilic Bronchial Inflammation Correlates with Clinical and Functional Findings in Patients with Noncystic Fibrosis Bronchiectasis

Background. Neutrophilic bronchial inflammation is a main feature of bronchiectasis, but not much is known about its relationship with other disease features. Aim. To compare airway inflammatory markers with clinical and functional findings in subjects with stable noncystic fibrosis bronchiectasis (NCFB). Methods. 152 NFCB patients (62.6 years; females: 57.2%) underwent clinical and functional cross-sectional evaluation, including microbiologic and inflammatory cell profile in sputum, and exhaled breath condensate malondialdehyde (EBC-MDA). NFCB severity was assessed using BSI and FACED criteria. Results. Sputum neutrophil percentages inversely correlated with FEV1 (P < 0.0001; rho = −0.428), weakly with Leicester Cough Questionnaire score (P = 0.068; rho = −0.58), and directly with duration of the disease (P = 0.004; rho = 0.3) and BSI severity score (P = 0.005; rho = 0.37), but not with FACED. Sputum neutrophilia was higher in colonized subjects, P. aeruginosa colonized subjects showing greater sputum neutrophilia and lower FEV1. Patients with ≥3 exacerbations in the last year showed a significantly greater EBC-MDA than the remaining patients. Conclusions. Sputum neutrophilic inflammation and biomarkers of oxidative stress in EBC can be considered good biomarkers of disease severity in NCFB patients, as confirmed by pulmonary function, disease duration, bacterial colonization, BSI score, and exacerbation rate.

RItA: The Italian severe/uncontrolled asthma registry

The Italian severe/uncontrolled asthma (SUA) web‐based registry encompasses demographic, clinical, functional, and inflammatory data; it aims to raise SUA awareness, identifying specific phenotypes and promoting optimal care.

Can Sputum Eosinophilia Be a Constant Feature in Severe Refractory Asthmatics? A 3-Year Longitudinal Study

In difficult-to-treat asthmatics, uncontrolled despite a high level of therapy and followed for 3 years with a mean number of sputum samples/patient = 10, sputum eosinophilia (≥3%) was observed in 87% of all sputum samples. Persistent sputum eosinophilia is a characteristic of severe uncontrolled asthma.

Focus on audiologic impairment in eosinophilic granulomatosis with polyangiitis

To evaluate the clinical features of audiologic impairment and its relationship with the nasal, vestibular, and rheumatologic profile in a cohort of patients with eosinophilic granulomatosis with polyangiitis (EGPA), formerly named Churg‐Strauss syndrome.

Sputum inflammatory cells in COPD patients classified according to GOLD 2011 guidelines.

Recently the definition of chronic obstructive pulmonary disease (COPD) severity, stated in 2001 by Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and based on forced expiratory volume in 1 s (FEV1) evaluation, has been considered inadequate to recognise all the multifaceted aspects of the disease. To overcome this limitation, 2011 GOLD recommendations suggested a new approach, which stratified COPD patients in four groups of severity (A, B, C, D) according to the level of symptoms (as assessed by either the modified Medical Research Council (mMRC) score or the COPD Assessment Test), the degree of airflow limitation (expressed as percentage of predicted forced expiratory volume in 1 s (FEV1) value) and the number of exacerbations in the previous year [1]. It is still matter of debate if this new classification helps to better understand the disease and improve COPD treatment and prognosis. Studies on the existing database have been published comparing the old with the new GOLD classifications, showing that GOLD 2011 classification adds new details on the phenotyping and on the prognosis of COPD [2–5]. Despite the many post hoc analyses performed on the large databases of the most important recent observational studies (ECLIPSE, CCLS, COPDgene), the demonstration that these different groups of GOLD 2011 classification are different for physiological and biological features is controversial. The A, B, C and D groups of the new GOLD classification are at least partly related to different COPD phenotypes http://ow.ly/Xgr8q

A valid option for asthma control: Clinical evidence on efficacy and safety of fluticasone propionate/formoterol combination in a single inhaler ☆

A good level of asthma control improves the quality of life of asthmatic patients and may prevent future risk in term of exacerbations and decline of pulmonary function. However, in a real-life setting, several factors contribute to generally low compliance to the treatment. A rapid-onset, long-lasting medication with few adverse effects may contribute to improve adherence to therapy, along with an effective patient education and a good physician-patient communication. Many clinical studies demonstrated the comparable efficacy of the new fluticasone propionate/formoterol (FP/F) combination in a single inhaler to other combinations of inhaled corticosteroids and β2agonists and the superiority of FP/F as compared to its individual components. Also the safety profile of this combination was encouraging in all studies, even at higher doses. By effectively and safely targeting both airway inflammation and smooth muscle dysfunction, the two pathological facets of asthma, and allowing the patient to adapt dose strength, FP/F combination in a single device represents a valid option to improve asthma control in patients with different levels of asthma severity.

Markers of small airway involvement and asthma control in patients with moderate to severe asthma.

Abbreviations: AaDO2, alveolar-arterial difference of oxygen; aADCO2, arterialalveolar difference of carbon dioxide; CalvNO, alveolar concentration of exhaled nitric oxide; CV, closing volume; FEF25%-75%, forced expiratory flow between 25% and 75% of forced vital capacity; JawNO, bronchial production of exhaled nitric oxide; DN2, the slope of phase 3 obtained by the single-breath nitrogen washout; VC, vital capacity. P < .05. The comparison between patients with controlled and noncontrolled asthma were The role of airway inflammation that involves the entire bronchial tree, from proximal to distal airways, in the pathogenesis of asthma is well understood. Small airways are the most peripheral airways, with an inner diameter less than 2 mm; it is in this region that oxygen and carbon dioxide exchanges take place. The contribution of the small airways to the development of the clinical features and functional impairment in asthma is incompletely understood, possibly because of the lack of definite noninvasive techniques for the study of small airways. The single-breath nitrogen washout test can be used to evaluate the presence of uneven ventilation, and this test has been found to discriminate between patients with severe asthma with and without recurrent exacerbations.1 This abnormal distribution of alveolar ventilation may result in a ventilation perfusion ratio ( _ V/ _ Q) imbalance, determining pulmonary gas exchange abnormalities thatmay reflect changes in the small airways.2 Bronchoconstriction induced by both methacholine (with a direct mechanism on smooth muscular cells) and adenosine monophosphate (with an indirect mechanism determining an inflammatory process) induces pulmonary gas exchange abnormalities as assessed by _ V/ _ Q3.3 Interestingly, after inhaled salbutamol, which actsmainly onproximal airways, these disturbances persisted. Other indexes of abnormal distribution of ventilation, including multiplebreath nitrogen washout and impulse oscillometry, have been used to assess small airway involvement,4 with some positive results in terms of either a distinction between symptomatic and nonsymptomatic patients or a correlation with other functional or inflammatory markers of airway involvement. Finally, biomarkers have also been used to detect small airway inflammation in asthma. Fractional exhaled nitric oxide (FENO) has been considered amarker of eosinophilic inflammation that involves small airways in asthma. Some asthmatic patients have the same level of functional large airway impairment, as assessed by forced expiratory volume in 1 second (FEV1), but with different clinical control of the disease in terms of symptoms and exacerbations. This different asthma control might be due to a different involvement of small airways. Even if this was the case, it would not be clear whether such involvement of small airways represents a different phenotype of asthma or just a marker of greater disease severity. To test the hypothesis that patients with uncontrolled and controlled asthma are better distinguished by markers of small airway involvement than by markers of large airway involvement, we selected a homogeneous group of asthmatic patients under regular treatment and compared markers of involvement of large (FEV1 and sputum eosinophil count) and small (single-breath test, alveolar-arterial gradients of oxygen and carbon dioxide, and

Focus on the Involvement of the Nose and Paranasal Sinuses in Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome): Nasal Cytology Reveals Infiltration of Eosinophils as a Very Common Feature

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing vasculitis that predominantly affects small- to medium-sized vessels. It is characterized by a wide spectrum of extrapulmonary symptoms, including sinonasal and paranasal sinus abnormalities. These are the most common features of this disease, constituting diagnostic criteria for EGPA. However, the actual clinical features, cellular mechanisms and impact on patients’ quality of life (QoL) are still a matter of study. Methods: Thirty-nine EGPA patients underwent multidimensional rhinological evaluations, including rhinofibroscopy, nasal cytology, and QoL questionnaires. This was coupled with respiratory and rheumatological assessments. Results: Twenty-eight patients were diagnosed with chronic rhinosinusitis (CRS). Of these, 18 had nasal polyposis (NP). Chronic rhinitis was diagnosed in 10 patients. Of these, 3 had allergic rhinitis (AR) and seven had non-AR (NAR). Overall, only 1 patient (2.6%) was normal. Nasal cytology showed that hypereosinophilia was present in 17/28 patients with CRS, 4/7 patients with NAR and all patients with AR. SNOT-22 and SF-36 showed a severe impact of nasal symptoms on QoL. No differences in asthma control or rheumatological patterns for EGPA were observed among patients with or without NP. Conclusions: Even when the rheumatological assessment scored EGPA “under control” according to the Birmingham Vasculitis Activity Score and Vasculitis Damage Index, sinonasal diseases and related nasal inflammatory processes were not controlled. Therefore, there is a need for clinical monitoring and targeted treatment to control the inflammatory processes and improve the QoL of EGPA patients.