The upper extremity functional index (UEFI): Italian validation in patients with Facioscapulohumeral muscular dystrophy.

PURPOSE: The aim of this study was to adapt the Upper Extremity Functional Index (UEFI) to an Italian population affected by Facioscapulohumeral muscular dystrophy (FSHD) by translating and validating this instrument in an Italian cohort. MATERIALS AND METHODS: Five Italian FSHD patients were interviewed regarding the form and content of the translated instrument. Subsequently, fifty-two patients were recruited for the validation purpose by serially completing the UEFI-IT and a battery of clinical assessments and questionnaires. Finally, a subset of thirty-nine patients underwent test-retest reliability. RESULTS: The Italian translation of the UEFI was highly relevant to patients, had a level of test-retest reliability from "good" to "excellent" (ICC = 0.90 with 95% confidence interval between 0.82 and 0.95), and a satisfactory internal consistency (Cronbach's alpha = 0.96). Participants confirmed the usefulness and clearness of the tool in cultural validity. In known group validity, the UEFI-IT was significantly lower in patients unable to walk (24.10 ± 11.33 vs 55.71 ± 13.98, p < .0001; AUC = 0.9631) and in patients with longer disease duration (43.43 ± 17.16 vs 58.14 ± 13.71, p = 0.0034; AUC = 0.7359). Finally, the concurrent validity showed strong associations between the UEFI-IT and motor assessments, pain perception, and quality-of-life evaluations. CONCLUSIONS: Overall, the UEFI-IT is an appropriate, valid, and reliable outcome measure for Italian-speaking FSHD patients.

It is important for the clinical community to have a valid instrument that can serially offer an accurate assessment of disability that involves questionnaires of the upper extremity functions.The Upper Extremity Functional Index (UEFI) is a deeply used region-specific patient-reported outcome measure (PROM) that investigates the patients' current upper extremity functional status.The Italian validation of UEFI (UEFI-IT) is a valid instrument that allows patients to report on the functional status of their upper limbs.The UEFI-IT provides clinicians with a valid and reliable outcome measure that is easy to use and applicable to a large number of clinical presentations and for both clinical practice and research.

Equating norms between the ALS Cognitive Behavioral Screen (ALS-CBS™) and the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) in non-demented ALS patients.

BACKGROUND: The present study aimed at deriving equating norms to estimate scores on the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) based on those on the ALS Cognitive Behavioral Screen (ALS-CBS™) in an Italian cohort of non-demented ALS patients. METHODS: ALS-CBS™ and ECAS scores of 293 ALS patients without frontotemporal dementia were retrospectively retrieved. Concurrent validity of the ALS-CBS™ towards the ECAS was tested by covarying for demographics, disease duration and severity, presence of C9orf72 hexanucleotide repeat expansion and behavioural features. A linear-smoothing equipercentile equating (LSEE) model was employed to derive ALS-CBS™-to-ECAS cross-walks. Gaps in LSEE-based estimation were managed via a linear regression-based equating approach. Equivalence between empirical and derived ECAS scores was tested via a two-one-sided test (TOST) procedure for the dependent sample. RESULTS: The ALS-CBS™ predicted the ECAS (ß = 0.75), accounting for the vast majority of its variance (60% out of an R2 = 0.71). Consistently, a strong, one-to-one linear association between ALS-CBS™ and ECAS scores was detected (r = 0.84; R2 = 0.73). The LSEE was able to estimate conversions for the full range of the ALS-CBS™, except for raw scores equal to 1 and 6 - for whom a linear equating-based equation was derived. Empirical ECAS scores were equivalent to those derived with both methods. DISCUSSION: Italian practitioners and researchers have been herewith provided with valid, straightforward cross-walks to estimate the ECAS based on ALS-CBS™ scores in non-demented ALS patients. Conversions herewith provided will help avoid cross-sectional/longitudinal inconsistencies in test adoption within research, and possibly clinical, settings.

The facioscapulohumeral muscular dystrophy - health index: Italian validation of a disease-specific measure of symptomatic burden.

PURPOSE: The aim of this study was to adapt the Facioscapulohumeral Muscular Dystrophy - Health Index (FSHD-HI) to an Italian population affected by FSHD by translating, validating, and testing this instrument in an Italian cohort. MATERIALS AND METHODS: Italian FSHD patients were interviewed regarding the form and content of the translated instrument. Subsequently, forty FSHD patients were recruited to test the reliability (Intraclass Correlation Coefficient, ICC for test-retest; and Cronbach's Alpha for Internal consistency), known groups (Mann-Whitney U test and Area Under the Curve, AUC) and concurrent validity (Pearson's and Spearman's Rank Correlation Coefficient) of the instrument by serially completing the FSHD-HI and an extensive set of tests measuring the neuromotor, psychological and cognitive functions, and perceived quality of life (QoL) aspects. RESULTS: The Italian translation of the FSHD-HI and its subscales were highly relevant to patients, had a high internal consistency (Cronbach's Alpha = 0.90), optimal test-retest reliability (ICC= 0.95), and was significantly associated with motor function, respiratory function, and QoL assessments. CONCLUSIONS: Overall, the Italian FSHD-HI is a valid and well-suited measurement of the multi-dimensional aspects of disease burden in FSHD patients.

Facioscapulohumeral muscular dystrophy (FSHD) negatively impacts the quality of life and increases the disease burden.It is important for the clinical community to have a valid instrument that can serially measure a patient's perception of their multifactorial disease burden in FSHD.The Facioscapulohumeral Muscular Dystrophy ­ Health Index (FSHD-HI) is a valid instrument that allows patients to provide their perspective regarding their current health state.FSHD-HI-IT provides a valid option for measuring multifactorial disease burden in Italian patients with FSHD during clinical trials.

Clinimetrics of the cognitive section of the Italian ALS Cognitive Behavioral Screen (ALS-CBS™).

BACKGROUND: The present study aimed at (1) providing further validity and reliability evidence for the Italian version of the cognitive section of the ALS Cognitive Behavioral Screen (ALS-CBS™) and (2) testing its diagnostics within an Italian ALS cohort, as well as at (3) exploring its capability to discriminate patients from healthy controls (HCs). METHODS: N = 293 non-demented ALS patients were administered the cognitive sections of the ALS-CBS™ and Edinburgh Cognitive and Behavioural ALS Screen (ECAS). N = 96 HCs demographically matched with N = 96 patients were also administered the cognitive section of the ALS-CBS™. In patients, factorial and construct validity, internal reliability, and diagnostics against a defective score on the cognitive section of the ECAS were tested. Case-control discrimination was assessed via a logistic regression. RESULTS: ALS-CBS™ cognitive subscales were underpinned by a simple, unidimensional structure, internally reliable (McDonald's ω = 0.74), and mostly related with ECAS executive and fluency scores (rs = 0.54-0.71). Both raw and age- and education-adjusted scores on the cognitive section of the ALS-CBS™ accurately detected ECAS-defined cognitive impairment (AUC = 0.80 and .88, respectively), yielding optimal error-based, information-based and unitary diagnostics. A cut-off of < 15.374 was identified on adjusted scores. The test was able to discriminate patients from HCs (p < 0.001). DISCUSSION: The cognitive section of the Italian ALS-CBS™ is a valid, reliable, and diagnostically sound ALS-specific screener for detecting frontotemporal, executive-/attentive-based cognitive inefficiency in non-demented ALS patients, being also able to discriminate them from normotypical individuals.

Standardization of the Italian ALS-CBS™ Caregiver Behavioral Questionnaire.

Background: The present investigation aimed at testing the psychometrics and diagnostics of the Italian version of the Caregiver Behavioral Questionnaire (CBQ) from the ALS Cognitive Behavioral Screen (ALS-CBS™), as well as its case-control discrimination, in a cohort of non-demented patients with ALS. Methods: The caregivers of N = 265 non-demented patients with ALS and N = 99 healthy controls (HCs) were administered the CBQ and the Edinburgh Cognitive and Behavioural ALS Screen-Carer Interview (ECAS-CI). For N = 98 patients, an in-depth behavioural/psychopathological assessment via the Frontal Behavioural Inventory (FBI), the Dimensional Apathy Scale (DAS), the State and Trait Anxiety Inventory-Form Y (STAI-Y), and the Beck Depression Inventory (BDI) was also available. Factorial and construct validity, internal reliability, and diagnostics against an abnormal ECAS-CI score were tested in patients. Case-control discrimination was explored through logistic regression. Results: The CBQ was internally reliable (McDonald's ω = 0.90) and underpinned by a simple, unidimensional structure; it converged with ECAS-CI, FBI, and DAS scores and diverged from STAI-Y and BDI ones. A cutoff of ≤ 33 accurately detected abnormal ECAS-CI scores (AUC = 0.85), yielding optimal error- and information-based diagnostics. The CBQ was independent of demographic and disease-related variables and discriminated patients from HCs (p < 0.001). Discussion: The Italian version of the CBQ from the ALS-CBS™ is a valid, reliable, diagnostically sound, and feasible screener for detecting frontotemporal-like behavioural changes in non-demented patients with ALS. Its adoption is thus recommended within clinical practice and research in the view of providing preliminary information on whether the administration of more extensive behavioural instruments is needed.

A preliminary comparison between ECAS and ALS-CBS in classifying cognitive-behavioural phenotypes in a cohort of non-demented amyotrophic lateral sclerosis patients.

To define the presence and type of frontotemporal dysfunction in amyotrophic lateral sclerosis (ALS), different screening tools have been created. Currently, the most used screening tests are the Edinburgh cognitive and behavioural ALS screen (ECAS) and the ALS cognitive behavioural screen (ALS-CBS). The objective of this study was to compare the ability of ECAS and ALS-CBS in classifying non-demented ALS patients according to Strong criteria. One-hundred and fifty-four in- and out-patients with an age > 18 and a definite or probable ALS diagnosis were recruited between September 2019 and February 2020 at NeMO Clinical Centre and at Istituto Auxologico Italiano in Milan and underwent the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and the ALS Cognitive Behavioural Screen (ALS-CBS). Exclusion criteria involved patients with a diagnosis of FTD, with a severe cognitive deterioration and/or an important behavioural impairment, with a significant psychiatric disorder or with the co-presence of another significant illness. The distribution of patients according to Strong criteria was different for ECAS and ALS-CBS and the degree of agreement between the two tests in terms of Cohen's Kappa coefficient resulted equal to 0.2047 with a 95% confidence limits interval between 0.1122 and 0.2973. This study for the first time compares the ability of ECAS and ALS-CBS in stratifying ALS patients. Further studies will be conducted to better understand the reasons underlying the differences between these two tests in classifying the different subtypes of fronto-temporal dysfunction in ALS.

Association of Clinically Evident Eye Movement Abnormalities With Motor and Cognitive Features in Patients With Motor Neuron Disorders.

BACKGROUND AND OBJECTIVES: Although oculomotor abnormalities (OMAs) are not usually considered prominent features of amyotrophic lateral sclerosis (ALS), they may represent potential clinical markers of neurodegeneration, especially when investigated together with cognitive and behavioral alterations. The aim of our study was to identify patterns of clinically evident OMAs in patients with ALS and to correlate such findings with cognitive-behavioral data. METHODS: Three consecutive inpatient cohorts of Italian patients with ALS and controls were retrospectively evaluated to assess the frequency of OMAs and cognitive-behavioral alterations. The ALS population was divided into a discovery cohort and a replication cohort. Controls included a cohort of cognitively impaired individuals and patients with Alzheimer disease (AD). Participants underwent bedside eye movement evaluation to determine the presence and pattern of OMAs. Cognitive assessment was performed with a standard neuropsychological battery (discovery ALS cohort and AD cohort) and the Italian Edinburgh Cognitive and Behavioural ALS Screen (ECAS) (replication ALS cohort). RESULTS: We recruited 864 individuals with ALS (635 discovery, 229 replication), 798 who were cognitively unimpaired and 171 with AD. OMAs were detected in 10.5% of our ALS cohort vs 1.6% of cognitively unimpaired controls (p = 1.2 × 10-14) and 11.4% of patients with AD (p = NS). The most frequent deficits were smooth pursuit and saccadic abnormalities. OMA frequency was higher in patients with bulbar onset, prominent upper motor neuron signs, and advanced disease stages. Cognitive dysfunction was significantly more frequent in patients with OMAs in both ALS cohorts (p = 1.1 × 10-25). Furthermore, OMAs significantly correlated with the severity of cognitive impairment and with pathologic scores at the ECAS ALS-specific domains. Last, OMAs could be observed in 35.0% of cognitively impaired patients with ALS vs 11.4% of patients with AD (p = 6.4 × 10-7), suggesting a possible involvement of frontal oculomotor areas in ALS. CONCLUSION: Patients with ALS showed a range of clinically evident OMAs, and these alterations were significantly correlated with cognitive, but not behavioral, changes. OMAs may be a marker of neurodegeneration, and bedside assessment represents a rapid, highly specific tool for detecting cognitive impairment in ALS.

The Spinal Muscular Atrophy Health Index: Italian validation of a disease-specific outcome measure.

Patient report outcome measures in Spinal Muscular Atrophy (SMA) represent a potential complement to observer rated scales which can be used to better understand treatment response. We developed, translated and validated an Italian version of the Spinal Muscular Atrophy Health Index (SMAHI), a disease-specific, patient reported outcome measure questionnaire, designed to estimate the patients' perception of disease burden. Test-retest reliability was assessed in 37 patients (16 children aged 12-17 and 21 adults) and was excellent in both cohorts. Internal consistency in an additional 98 patients (24 children, 74 adults) was also excellent (Cronbach's alpha = 0.93 and 0.91 respectively). In children the highest level of disease burden was generated from lower limb dysfunction and fatigue as well as their perception of decreased performance in social situations. Most patients in the adult cohort were sitters and complained of problems with upper limb functions as well as of fatigue. The SMAHI-IT was also able to differentiate between SMA types according to diseases severity. The results of our study demonstrate that the SMAHI can be considered a marker of disease-specific burden in patients with SMA with a high test-retest reliability and internal validity in Italian patients aged 12 and older.

Ocular Involvement Occurs Frequently at All Stages of Amyotrophic Lateral Sclerosis: Preliminary Experience in a Large Italian Cohort.

BACKGROUND AND PURPOSE: The study aimed to obtain optometric findings of amyotrophic lateral sclerosis (ALS) patients in different stages of the disease, and to determine the relation between ocular data and ALS-related features; that is, functional and cognitive impairment and staging. METHODS: The optometric protocol included tests of the ocular motility [broad-H test and Northeastern State University College of Optometry (NSUCO) test], near point of convergence (NPC), error refraction, best-corrected visual acuity, and binocular visual alignment, and an ocular symptoms questionnaire. The functional measures included the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-r) and Milano-Torino staging (MiToS), and cognitive impairment was assessed using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Demographic and clinical features were also collected, including whether the patients used an eye-tracking communication device (ETCD). RESULTS: Two-hundred consecutive ALS patients (median age of 64 years, 118 males and 82 females) in different stages of disease were recruited. Nearly 70% of patients reported at least one ocular symptom, and the use of an ETCD was found to be significantly related to the presence of most symptoms. Moreover, the severely symptomatic group was characterized by significantly lower ALSFRS-r total and subscale scores, and higher MiToS. Abnormal NPC values were significantly related to lower ALSFRS-r total and bulbar-subscale scores. Patients with acceptable NSUCO test values exhibited significantly higher ECAS scores. CONCLUSIONS: The presence of ocular alteration in patients in different stages of ALS supports the idea that this is a multisystem disorder and emphasizes the importance of optometric evaluations in multidisciplinary assessments to address ocular impairment early in the disease process.

The development of an augmented reality device for the autonomous management of the electric bed and the electric wheelchair for patients with amyotrophic lateral sclerosis: a pilot study.

PURPOSE: The main aim of this Human Centred Design project was to develop the Environment COntrol in Amyotrophic Lateral Sclerosis (ECO-ALS) System, a new device which could improve ALS patient's autonomy in controlling the environment. Moreover, we verified the feasibility and usability of this technology in ALS patients in advanced stages of the disease. MATERIAL AND METHODS: Twelve ALS patients in advanced disease stage were recruited, two patients for the development phase and ten patients and their caregivers for the two weeks' trial phase. We evaluated the impact of the ECOALS system by administering the Psychosocial Impact of Assistive Devices Scale (PIADS), the Individual Prioritised Problem Assessment (IPPA), the McGill Quality of Life Questionnaire (MQOL) and the Caregiver Burden Inventory (CBI). RESULTS: In the trial phase, patients were very satisfied for having recovered their autonomy in the management of the EAB, that enabled patients to reduce calls to their caregivers to change their bed position. The IPPA questionnaire showed a significant improvement in patients' participation and management of the system. Moreover, the PIADS questionnaire showed that patients perceived a progress in competence, adaptability and areas of self-esteem, confirming a positive psychosocial impact of the patients' assistance device. CONCLUSION: The project has collected some useful information for technological system development to face the need for autonomy ALS patients. Patients were satisfied with the tested aids and were interested in the future developments. Further studies are needed to improve the system and overcome some technical problems that occurred during the project.IMPLICATIONS FOR REHABILIATIONThe ECO-ALS system seems to improve the patients' perceived autonomy.The ECO-ALS system seems to improve the patients' perceived progress in competence, adaptability and areas of self-esteem, confirming a positive psychosocial impact of the assistance device.The ECO-ALS system seems to improve the patients' perceived quality of life.Patients were satisfied with the tested aids and were interested in the future developments.

Unraveling Moral Reasoning in Amyotrophic Lateral Sclerosis: How Emotional Detachment Modifies Moral Judgment.

In the last decade, scientific literature provided solid evidence of cognitive deficits in amyotrophic lateral sclerosis (ALS) patients and their effects on end-life choices. However, moral cognition and judgment are still poorly investigated in this population. Here we aimed at evaluating both socio-cognitive and socio-affective components of moral reasoning in a sample of 28 ALS patients. Patients underwent clinical and neuropsychological evaluation including basic cognitive and social cognition measures. Additionally, we administered an experimental task including moral dilemmas, with instrumental and incidental conditions. Patients' performances were compared with a control group [healthy control (HC)], including 36 age-, gender-, and education-matched healthy subjects. Despite that the judgment pattern was comparable in ALS and HC, patients resulted less prone to carry out a moral transgression compared to HC. Additionally, ALS patients displayed higher levels of moral permissibility and lower emotional arousal, with similar levels of engagement in both instrumental and incidental conditions. Our findings expanded the current literature about cognitive deficits in ALS, showing that in judging moral actions, patients may present non-utilitarian choices and emotion flattening. Such a decision-making profile may have relevant implications in applying moral principles in real-life situations and for the judgment of end-of-life treatments and care in clinical settings.

Taste changes in amyotrophic lateral sclerosis and effects on quality of life.

The primary aim of the study is to evaluate possible taste changes in a cohort of amyotrophic lateral sclerosis patients (pALS) with dysphagia, focusing on eventual psychological and quality of life (QoL) implications. The second aim is to evaluate the changes of QoL following the use of a specific device that provides food flavour. Thirty-two ALS patients were recruited and divided into two groups: subjects feeding only through enteral tube (ET) and subjects still eating by oral way (OW). A specific set of questionnaires was selected and adapted to investigate possible changes of taste and the impact on psychological status and QoL. Moreover, a specific device that provides food flavours in a safety manner was applied to all patients. We found a perceived reduction of taste in ALS patients, in particular in the ET group. All patients showed a strong interest in the preservation of taste, and its loss negatively related to their QoL. The use of the flavour device improved the perceived QoL showing no side effects, even in the ET group. For the first time, our study revealed changes in taste perception in a cohort of ALS patients and the negative consequences that these changes have on psychological status and QoL. Furthermore, the positive effects of the device used to provide flavours suggest a possible rehabilitative effect, which should be better evaluated and confirmed in further studies.

The Myotonic Dystrophy Health Index: Italian validation of a disease-specific outcome measure.

The Myotonic Dystrophy Health Index (MDHI) is a disease-specific, self-reported outcome measure that assesses total disease burden and 17 areas of Myotonic Dystrophy type 1 (DM1) specific health. This study translated the MDHI into Italian and validated the instrument using a cohort of Italian DM1 patients. Italian DM1 patients were interviewed regarding the form and content of the instrument. Thirty-eight DM1 patients were subsequently recruited to test the reliability and concurrent validity of the instrument by serially completing the MDHI and a battery of clinical tests. Lastly, we determined the internal consistency of the Italian MDHI and each of its subscales. The internal consistency was excellent in the total Italian MDHI score and acceptable in all of its subscales; the test-retest reliability was high (intraclass correlation coefficient = 0.95); Italian MDHI total scores and subscales were associated with neuromuscular function, cognitive and social health, respiratory function, and quality of life. Overall, the Italian MDHI is valid and well suited to measure the multi-dimensional aspects of disease burden in Myotonic Dystrophy clinical trials.

The Role of Single-Subject Brain Metabolic Patterns in the Early Differential Diagnosis of Primary Progressive Aphasias and in Prediction of Progression to Dementia.

BACKGROUND AND OBJECTIVE: Primary progressive aphasia (PPA) is a clinical syndrome due to different neurodegenerative conditions in which an accurate early diagnosis needs to be supported by a reliable diagnostic tool at the individual level. In this study, we investigated in PPA the FDG-PET brain metabolic patterns at the single-subject level, in order to assess the case-to-case variability and its relationship with clinical-neuropsychological findings. MATERIAL AND METHODS: 55 patients (i.e., 11 semantic variant/sv-PPA, 19 non fluent variant/nfv-PPA, 17 logopenic variant/lv-PPA, 3 slowly progressive anarthria/SPA, and 5 mixed PPA/m-PPA) were included. Clinical-neuropsychological information and FDG-PET data were acquired at baseline. A follow-up of 27.4±12.55 months evaluated the clinical progression. Brain metabolism was analyzed using an optimized and validated voxel-based SPM method at the single-subject level. RESULTS: FDG-PET voxel-wise metabolic assessment revealed specific metabolic signatures characterizing each PPA variant at the individual level, reflecting the underlying neurodegeneration in language networks. Notably, additional dysfunctional patterns predicted clinical progression to specific dementia conditions. In the case of nfv-PPA, a metabolic pattern characterized by involvement of parietal, subcortical and brainstem structures predicted progression to a corticobasal degeneration syndrome or to progressive supranuclear palsy. lv-PPA and sv-PPA cases who progressed to Alzheimer's disease and frontotemporal dementia at the follow-up presented with extended bilateral patterns at baseline. DISCUSSION: Our results indicate that FDG-PET voxel-wise imaging is a valid biomarker for the early differential diagnosis of PPAs and for the prediction of progression to specific dementia condition. This study supports the use of FDG-PET imaging quantitative assessment in clinical settings for a better characterization of PPA individuals and prognostic definition of possible endo-phenotypes.

The effect of fexofenadine on expression of intercellular adhesion molecule 1 and induction of apoptosis on peripheral eosinophils.

The role of eosinophils in the pathogenesis of allergic disorders has been established by several studies. Recently, it has been suggested that second-generation antihistamines, widely used to relieve allergic symptoms, may have anti-inflammatory effects. To assess the possible anti-inflammatory activity of fexofenadine, a selective H1-receptor antagonist, we evaluated its capacity to modulate the expression of adhesion molecules leukocyte function-associated antigen (LFA) 1 and intracellular adhesion molecule (ICAM) 1 on eosinophil surface and to induce apoptosis of eosinophils. To analyze the expression of adhesion molecules, eosinophils from healthy donors were cultured in the presence of interferon gamma and tumor necrosis factor alpha with various concentrations of fexofenadine, incubated with monoclonal antibodies anti-ICAM-1 and LFA-1 and then analyzed by flow cytometry. To evaluate apoptosis of eosinophils, cells stimulated with interleukin-5, in the presence of different concentrations of fexofenadine, have been incubated with a phosphatidylserine-binding protein (annexin V) fluorescein isothiocyanate conjugated and then analyzed by flow cytometry. Apoptosis was evaluated as a percentage of annexin V+ cells. In this study, fexofenadine did not cause any significant changes in the expression of LFA-1 but was shown to be able to inhibit the expression of ICAM-1 at concentrations between 10(-3) and 10(-4) M. Moreover, concentrations of fexofenadine from 10(-3) to 6 x 10(-4) M induced a significant increment in the percentage of apoptotic cells. Our findings indicate the possibility of obtaining relevant anti-inflammatory pharmacologic effects, other than antihistamine activity, by fexofenadine, such as inhibition of ICAM-1 expression and induction of eosinophil apoptosis.

Impact of intranasal budesonide on immune inflammatory responses and epithelial remodeling in chronic upper airway inflammation.

BACKGROUND: Histologic and immunohistologic features of nasal polyps (NP) are similar to those observed in asthma, thus suggesting a similar immunopathology. OBJECTIVE: The primary objective of this study was to further understand the anti-inflammatory and immunoregulatory effects of locally delivered corticosteroids. To this end, the effect of intranasal budesonide on the expression of specific cytokines, lymphocyte subsets, and epithelial remodeling in this model of airway tissue inflammation were studied. METHODS: We used immunohistochemical techniques to examine nasal mucosae (NM) from healthy individuals and nasal polyp (NP) tissues from patients with nasal polyposis obtained before and after intranasal budesonide treatment. RESULTS: First, the density of CD8(+) cells was markedly increased in NP tissues after intranasal budesonide treatment from 16.1 +/- 8.4 (M +/- SEM) per mm(2) to 39.9 +/- 24.1. Second, the density of cells immunoreactive for IL-4, IL-5, IFN-gamma, IL-12, and TGF-beta in NP was significantly greater than in control NM tissues. The density of IL-4(+) and IL-5(+) cells in NP tissues significantly decreased after budesonide treatment from 40 +/- 12 to 17.8 +/- 8 and from 19.3 +/- 11 to 10.4 +/- 7, respectively. In contrast, the density of IFN-gamma(+) and IL-12(+) cells remained unchanged. In addition, we found that the density of TGF-beta(+) cells significantly increased after intranasal budesonide from 18 +/- 5 to 41 +/- 9. Third, damage to the entire length of the NP epithelium was quantified using a grading system. The epithelium of untreated NP was substantially damaged; remarkable epithelial restitution with no apparent changes in stromal collagen deposition was observed after intranasal budesonide treatment. CONCLUSIONS: These findings demonstrate that intranasal budesonide induced an increase in CD8 population and a selective regulatory effect on tissue cytokine expression. Furthermore, intranasal budesonide promoted epithelial remodeling. We hypothesize that these immunoregulatory and remodeling effects elicited by steroids might be, at least in part, mediated by the induction of TGF-beta.