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Highlights • Consolidative radiotherapy (RT) has been shown to improve overall survival in oligometastatic non-small cell lung cancer (NSCLC). • We quantified the costs of RT in oligometastatic NSCLC, by applying time-driven activity-based costing (TDABC). • This analysis uses TDABC to estimate the relative internal costs of various RT strategies associated with treating oligometastatic NSCLC. • This methodology will become increasingly relevant in context of the anticipated mandate of alternative/bundled payment models., Background: Consolidative radiotherapy (RT) has been shown to improve overall survival in oligometastatic non-small cell lung cancer (NSCLC), as demonstrated by a growing number of prospective trials. Objective: We quantified the costs of delivery of consolidative RT for common clinical pathways associated with treating oligometastatic NSCLC, by applying time-driven activity-based costing (TDABC) methodology. Methods: Full cycle costs were evaluated for 4 consolidative treatment regimens: (Regimen #1) 10-fraction 3D conformal radiation therapy (3D-CRT) as palliation of a distant site; (#2) 15-fraction intensity-modulated RT (IMRT) to the primary thoracic disease; (#3) 15-fraction IMRT to the primary plus 4-fraction stereotactic ablative radiotherapy (SABR) to a single oligometastatic site; and (#4) 15-fraction IMRT to the primary plus two courses of 4-fraction SABR for two oligometastatic sites. Results: For each of the four treatment regimens, personnel represented a greater proportion of total cost when compared with equipment, totaling 61.0%, 65.9%, 66.2%, and 66.4% of the total cost of each care cycle, respectively. In total, a 10-fraction regimen of 3D-CRT to a distant site represented just 37.2% of the total cost of the most expensive course. Compared to total costs for 15-fraction IMRT alone, each additional sequential course of 4-fraction SABR imparted a cost increase of 43%. Conclusion: This analysis uses TDABC to estimate the relative internal costs of various RT strategies associated with treating oligometastatic NSCLC. This methodology will become increasingly relevant to each organization in context of the anticipated mandate of alternative/bundled payment models for radiation oncology by the Centers for Medicare and Medicaid Services.

Purpose We integrated a brachytherapy procedural workflow within an existing diagnostic 3.0-T (3T) MRI suite. This setup facilitates intraoperative MRI guidance for optimal applicator positioning, particularly for interstitial needle placements in gynecologic cases with extensive parametrial involvement. Methods and Materials Here we summarize the multidisciplinary collaboration, equipment, and supplies necessary to implement an intraoperative MRI-guided brachytherapy program; outline the operational workflow via process maps; and address safety precautions. We evaluate internal resource utilization associated with this progressive approach via time-driven activity-based costing methodology, comparing institutional costs to that of a traditional workflow (within a CT suite, followed by separate postprocedure MRI) over a single brachytherapy procedural episode. Results Resource utilization was only 15% higher for the intraoperative MRI-based workflow, attributable to use of the MRI suite and increased radiologist effort. Personnel expenses were the greatest cost drivers for either workflow, accounting for 76–77% of total resource utilization. However, use of the MRI suite allows for potential cost-shifting opportunities from other resources, such as CT, during the procedural episode. Improvements in process speed can also decrease costs: for each 10% decrease in case duration from baseline procedure time, total costs could decrease by roughly 8%. Conclusions This analysis supports the feasibility of an intraoperative MRI-guided brachytherapy program within a diagnostic MRI suite and defines many of the resources required for this procedural workflow. Longer followup will define the full utility of this approach in optimizing the therapeutic ratio for gynecologic cancers, which may translate into lower costs and higher value with time, over a full cycle of care.

Purpose The purpose of this study was to investigate the utility of a novel MRI-positive line marker, composed of C4:S (cobalt chloride–based contrast agent) encapsulated in high-density polyethylene tubing, in permitting dosimetry and treatment planning directly on MRI. Methods and Materials We evaluated the clinical feasibility of the C4:S line markers in nine sequential brachytherapy procedures for gynecologic malignancies, including six tandem-and-ovoid and three interstitial cases. We then quantified the internal resource utilization of an intraoperative MRI-guided procedural episode via time-driven activity-based costing, identifying opportunities for cost-containment with use of the C4:S line markers. Results The C4:S line markers demonstrated the strongest positive signal visibility on 3D constructive interference in steady state (CISS)/FIESTA-C followed by T1-weighted sequences, permitting accurate delineation of the applicator lumen and thus the source path. These images may be fused along with traditional T2-weighted sequences for optimal tumor and anatomy contouring, followed by treatment planning directly on MRI. By eliminating postoperative CT for fusion and applicator registration from the procedural episode, use of the C4:S line markers could decrease workflow time and lower total delivery costs per procedure. Conclusions This analysis supports the clinical utility and value contribution of the C4:S line markers, which permit accurate MRI-based dosimetry and treatment planning, thereby eliminating the need for postoperative CT for fusion and applicator registration.

Purpose The purpose of this study was to quantify the cost of resources required to deliver adjuvant radiation therapy (RT) for high- to intermediate-risk endometrial cancer using time-driven activity-based costing (TDABC). Methods and Materials Comparisons were made for three and five fractions of vaginal cuff brachytherapy (VCB), 28 fractions of intensity-modulated radiation therapy (IMRT), and combined modality RT (25-fraction IMRT followed by 2-fraction VCB). Process maps were developed representing each phase of care. Salary and equipment costs were obtained to derive capacity cost rates, which were multiplied by process times and summed to calculate total costs. Costs were compared with 2018 Medicare physician fee schedule reimbursement. Results Full cycle costs for 5-fraction VCB, IMRT, and combined modality RT were 42%, 61%, and 93% higher, respectively, than for 3-fraction VCB. Differences were attributable to course duration and number of fractions/visits. Accumulation of cost throughout the cycle was steeper for VCB, rising rapidly within a shorter time frame. Personnel cost was the greatest driver for all modalities, constituting 76% and 71% of costs for IMRT and VCB, respectively, with VCB requiring 74% more physicist time. Total reimbursement for 5-fraction VCB was 40% higher than for 3-fractions. Professional reimbursement for IMRT was 31% higher than for 5-fraction VCB, vs. IMRT requiring 43% more physician TDABC than 5-fraction VCB. Conclusions TDABC is a feasible methodology to quantify the cost of resources required for delivery of adjuvant IMRT and brachytherapy and produces directionally accurate costing data as compared with reimbursement calculations. Such data can inform institution-specific financial analyses, resource allocation, and operational workflows.

PURPOSE: Several treatment options for spinal metastases exist, including multiple radiation therapy (RT) techniques: three-dimensional (3D) conventional RT (3D-RT), intensity-modulated RT (IMRT), and spine stereotactic radiosurgery (SSRS). Although data exist regarding reimbursement differences across regimens, differences in provider care delivery costs have yet to be evaluated. We quantified institutional costs associated with RT for spinal metastases, using a time-driven activity-based costing model. METHODS: Comparisons were made between (1) 10-fraction 3D-RT to 30 Gy, (2) 10-fraction IMRT to 30 Gy, (3) 3-fraction SSRS (SSRS-3) to 27 Gy, and (4) single-fraction SSRS (SSRS-1) to 18 Gy. Process maps were developed from consultation through follow-up 30 days post-treatment. Process times were determined through panel interviews, and personnel costs were extracted from institutional salary data. The capacity cost rate was determined for each resource, then multiplied by activity time to calculate costs, which were summed to determine total cost. RESULTS: Full-cycle costs of SSRS-1 were 17% lower and 17% higher compared with IMRT and 3D-RT, respectively. Full-cycle costs for SSRS-3 were only 1% greater than 10-fraction IMRT. Technical costs for IMRT were 50% and 77% more than SSRS-3 and SSRS-1. In contrast, personnel costs were 3% and 28% higher for SSRS-1 than IMRT and 3D-RT, respectively ( P < .001). CONCLUSIONS: Resource utilization varies significantly among treatment options. By quantifying provider care delivery costs, this analysis supports the institutional resource efficiency of SSRS-1. Incorporating clinical outcomes with such resource and cost data will provide additional insight into the highest value modalities and may inform alternative payment models, operational workflows, and institutional resource allocation.

How do cultural, artistic, and media practices participate in the distribution of affects and feelings? How, as media participants, can we use these affects and feelings in strategies of persistenc...

Aim: To explore the clinical presentation, course, treatment and impact of early treatment in patients with remethylation disorders from the European Network and Registry for Homocystinurias and Methylation Defects (E-HOD) international web-based registry. Results: This review comprises 238 patients (cobalamin C defect n = 161; methylenetetrahydrofolate reductase deficiency n = 50; cobalamin G defect n = 11; cobalamin E defect n = 10; cobalamin D defect n = 5; and cobalamin J defect n = 1) from 47 centres for whom the E-HOD registry includes, as a minimum, data on medical history and enrolment visit. The duration of observation was 127 patient years. In 181 clinically diagnosed patients, the median age at presentation was 30 days (range 1 day to 42 years) and the median age at diagnosis was 3.7 months (range 3 days to 56 years). Seventy-five percent of pre-clinically diagnosed patients with cobalamin C disease became symptomatic within the first 15 days of life. Total homocysteine (tHcy), amino acids and urinary methylmalonic acid (MMA) were the most frequently assessed disease markers; confirmatory diagnostics were mainly molecular genetic studies. Remethylation disorders are multisystem diseases dominated by neurological and eye disease and failure to thrive. In this cohort, mortality, thromboembolic, psychiatric and renal disease were rarer than reported elsewhere. Early treatment correlates with lower overall morbidity but is less effective in preventing eye disease and cognitive impairment. The wide variation in treatment hampers the evaluation of particular therapeutic modalities. Conclusion: Treatment improves the clinical course of remethylation disorders and reduces morbidity, especially if started early, but neurocognitive and eye symptoms are less responsive. Current treatment is highly variable. This study has the inevitable limitations of a retrospective, registry-based design. © 2018 SSIEM

Assessing and monitoring respiratory muscle function is crucial in patients with Amyotrophic Lateral Sclerosis, since impaired function can lead to either ventilatory failure or respiratory tract infection. Spirometry, diffusing capacity of the lung, breathing pattern, sleep study, blood gas analysis and respiratory muscle strength tests, as well as cough peak flow and cough expiratory volume measurements can provide relevant information on ventilatory function and cough efficacy. With regard to respiratory muscle strength testing, the rational approach consists in starting with volitional and non-invasive tests and later using invasive and non-volitional tests. This review focuses on both ventilatory and respiratory muscle strength testing, in order to undertake a timely treatment of respiratory failure and/or impaired cough efficacy. So far, the current literature has not highlighted any gold standard which stipulates when to commence ventilation and cough support in patients with Amyotrophic Lateral Sclerosis. A composite set of clinical and functional parameters is required for treatment scheduling to monitor lung involvement and follow-up in these patients.

e18305 Background: The cost of a full cycle of radiation therapy at MD Anderson Cancer Center has not been determined using a bottom-up measurement approach. Due to the complexity and variation in clinical processes, typical costing strategies do not provide the level of detail necessary to evaluate the value equation, defined as outcomes over cost. To address this limitation, we designed and implemented a practice-wide Time-Driven Activity-Based Costing (TDABC) strategy to capture our total direct cost of care for all treatment modalities within each of 9 disease site-specific services. Methods: Process maps were created for each of the 9 disease site-specific services. Care delivery times were captured by treatment modality for each service as determined by multidisciplinary teams routinely performing each step of the process. The data were entered into a standardized tool, which calculated step costs based upon capacity cost rates for each human resource. The costing tool also calculated total direct labor costs for specific treatment plans based on modality, complexity, and fractionation. Results: The analysis took six months to complete and required the use of approximately 1,000 administrative hours, 250 physician hours, 250 clinical staff hours and 100 medical physics hours. Approximately 17 process maps were created for each of the 9 services with each process map receiving further analysis based upon radiation treatment modality. As a result of observed variation in costs between disease-site services, best practices were identified and 15 standardization opportunities were discovered. Additionally, the cost-benefit analysis between high profile modalities within each disease-site service, such as Proton Therapy and Intensity Modulated Radiation Therapy (IMRT) on the Head and Neck service, were easier to complete. Conclusions: Time-Driven Activity-Based Costing is a valid method for calculating direct costs in a large academic radiation oncology practice. Standardized clinical outcome data can be used to complete the value equation and ultimately provide insight for better clinical and administrative decision making.

It is not well-studied how the ubiquitous neuromodulator adenosine (ADO) affects mammalian locomotor network activities. We analyzed this here with focus on roles of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)-sensitive A(1)-type ADO receptors. For this, we recorded field potentials from ventral lumbar nerve roots and electrically stimulated dorsal roots in isolated newborn rat spinal cords. At ≥ 25μM, bath-applied ADO slowed synchronous bursting upon blockade of anion-channel-mediated synaptic inhibition by bicuculline (20 μM) plus strychnine (1 μM) and this depression was countered by DPCPX (1 μM) as tested at 100 μM ADO. ADO abolished this disinhibited rhythm at ≥ 500 μM. Contrary, the single electrical pulse-evoked dorsal root reflex, which was enhanced in bicuculline/strychnine-containing solution, persisted at all ADO doses (5 μM-2 mM). In control solution, ≥ 500 μM ADO depressed this reflex and pulse train-evoked bouts of alternating fictive locomotion; this inhibition was reversed by 1 μM DPCPX. ADO (5 μM-2 mM) did not depress, but stabilize alternating fictive locomotion evoked by serotonin (10 μM) plus N-methyl-d-aspartate (4-5 μM). Addition of DPCPX (1μM) to control solution did not change either the dorsal root reflex or rhythmic activities indicating lack of endogenous A(1) receptor activity. Our findings show A(1) receptor involvement in ADO depression of the dorsal root reflex, electrically evoked fictive locomotion and spontaneous disinhibited lumbar motor bursting. Contrary, chemically evoked fictive locomotion and the enhanced dorsal root reflex in disinhibited lumbar locomotor networks are resistant to ADO. Because ADO effects in standard solution occurred at doses that are notably higher than those occurring in vivo, we hypothesize that newborn rat locomotor networks are rather insensitive to this neuromodulator.

We examined the staining characteristics and degranulation of mast cells in bronchial biopsy specimens taken by fiberoptic bronchoscopy from 13 stable asthmatic patients and eight normal nonsmoking subjects. Specimens were fixed in periodate-lysine-paraformaldehyde, embedded in glycol methacrylate, and stained with toluidine blue (2%) for 30 min (pH 2.7) and 7 days (pH 0.5). The number of mast cells in the epithelium and in the lamina propria was counted under light microscopy. In addition, the distribution of mast cells with different granule contents, arbitrarily defined as degranulated or partly degranulated and fully granulated, was estimated at the two levels. In asthmatic subjects, the number of mast cells in the epithelium after either staining method was significantly higher compared with that in control subjects. The number of mast cells in the lamina propria, but not in the epithelium, was significantly higher after 7 days compared with 30-min toluidine blue stain both in asthmatic (135.6/mm2 versus 74.8/mm2; p < 0.001) and control subjects (121.5/mm2 versus 71.5/mm2; p < 0.01). There was evidence of a progressive mast cell degranulation when moving toward the airway lumen in both groups. However, degranulation was more evident in asthmatic subjects. In both groups, granulated mast cells were absent in the epithelium, whereas in the lamina propria granulated mast cells were approximately one-third of total in asthmatic and two-thirds of total in normal subjects. These observations suggest that mast cells in human bronchial mucosa are heterogeneous with respect to histochemical characteristics. They provide evidence that degranulation of mast cells occurs in both asthmatic and normal subjects and that degranulation is greater in asthmatics.

Increasing evidence suggests that plastic changes underlying skill learning may occur at early stages of neural processing. However, whether visual perceptual learning (PL) is accompanied by neuronal plasticity phenomena in the primary visual cortex (V1) is yet unknown. Here, we provide the first evidence that practice with specific visual stimuli (gratings) induces long-term potentiation (LTP) of synaptic responses in the rat V1. We report that in rats which have improved through practice their ability to discriminate between two gratings of different spatial frequency, the input/output curves of field potentials evoked in layers II-III of V1 slices by stimulation of either vertical and horizontal connections are shifted leftward compared to controls. Thus, visual PL is followed by potentiation of synaptic transmission both in vertical and horizontal connections (mimicry). We next show that this increase in intracortical connectivity gain is paralleled by LTP-like phenomena caused by the learning process: indeed, visual PL occludes further LTP (occlusion). Mimicry and occlusion are not present in the primary somatosensory cortex of rats trained with PL. These results demonstrate that LTP accompanies PL and highlight the notion that learning can occur at processing stages as early as the primary sensory cortices.

The definition of asthma has evolved from that of an episodic disease characterized by reversible airways constriction to a chronic inflammatory disease of the airways, with at least partially reversible airway constriction. Increasing evidence supports the notion that small and large airways play a central role in asthma pathophysiology with regard to inflammation, remodeling and symptoms. The contribution of the distal airways to the asthma phenotype carries implications for the delivery of inhaled medications to the appropriate areas of the lung and for the monitoring of the response to asthma treatment. Asthma control is evaluated on the basis of symptoms, lung function and exacerbations. However, evidence suggests that dissociation between lung function and respiratory symptoms, quality of life and airway inflammation exists. In this study, common spirometric parameters offer limited information with regard to the peripheral airways, and it is therefore necessary to move beyond FEV(1). Several functional parameters and inflammatory markers, which are discussed in the present study, can be employed to evaluate distal lung function. In this study, extrafine formulations deliver inhaled drugs throughout the bronchial tree (both large and small airways) and are effective on parameters that directly or indirectly measure air trapping/airway closure.

Cough flows and pressures were measured during cough augmentation in healthy subjects and patients with bulbar and nonbulbar amyotrophic lateral sclerosis. Manual assistance increased flow 11% in bulbar (p < 0.01) and 13% in nonbulbar (p < 0.001) patients. Mechanical insufflation-exsufflation increased flow 17% in healthy subjects (p < 0.05), 26% (p < 0.001) in bulbar, and 28% (p < 0.001) in nonbulbar patients. The greatest improvements were in patients with the weakest coughs. Patient group and level of weakness influenced the effect of augmentation.

Air pollution is one of the world's most serious environmental problems. It has been common knowledge for many years now that the lung is one of the main target organs of environmental agents. Over the last ten years, in particular, lung diseases have increased dramatically and the literature on the subject reports high death rates from lung cancer and an increased incidence of bronchial asthma and chronic obstructive pulmonary disease (COPD). These respiratory diseases are also caused by exposure to environmental agents, especially air pollution. Outdoor pollution is related to many compounds and, in assessing the air-borne pollutants and their association with respiratory damage, the role of particulate matter (PM) is of major importance. In addition to outdoor pollution, indoor pollution also exists and consists of environmental substances usually found outside which enter the internal environment, and/or of locally produced substances. Air pollution exposure involves the contact of pollutants with the respiratory tract, such exposure being measured according to two parameters: intensity and duration. Generally speaking, the pathogenic effects of environmental pollution on the organism fall into two categories: acute, or short-term effects, and long-term effects, depending on the time required from exposure to the manifestation of its effect. Short-term effects consist of irritant symptoms affecting the airways with different degrees of severity, while long-term effects, related to chronic exposure, are associated with chronic respiratory diseases, and unremitting symptoms such as coughing, wheezing, etc. Moreover, air irritants can give rise to inflammatory damage of the mucous membrane of the airways, thereby making it more susceptible to various types of allergens. In conclusion, air pollution is an important etiological factor for many chronic respiratory disorders, such as bronchial asthma and COPD. Prevention programs and early treatments are essential in an attempt to block the clinical-functional deterioration caused by these respiratory diseases.

Bronchial asthma is one of the most common chronic diseases in the world and can affect people of all ages. In the last few years there has been a considerable improvement in the etiopathogenetic knowledge of the disease and extremely effective anti-asthmatic drugs are available. However, asthma-related morbidity and mortality are increased, especially in Western countries. In an attempt to reverse this negative trend, for a number of years national and international guidelines on asthma have been published all over the world. These guidelines have the aim of improving asthma diagnosis and treatment and of conveying a fundamental educational message both to health workers and to patients and their families. From the data in the literature it can be clearly seen that only through the application of valid educational programs is it possible for asthmatics to improve their knowledge of the disease and to understand how they can look after themselves by a careful evaluation of their own symptoms and respiratory function. They should also be aware of the drugs available for the treatment of both acute asthmatic crises and chronic asthma, but especially of the fact that this chronic inflammatory affection can be fully treated. In particular, an educational program organized with groups of maximum 10-12 people attending 2 lessons and with helpful training tools, can increase significantly asthma knowledge, treatment compliance and patient self-management. The aim of this review is to highlight the importance of educational programs and those obscure areas which slow down their large scale application and universal acceptance.

The deformation mechanisms and energy absorption capability of polystyrene foams and polycarbonate shells for protective helmets are experimentally studied with the aim of developing a comprehensive constitutive law to be implemented into FEM codes for impact analysis. Expanded polystyrene (EPS) of different densities are considered. Tensile and bending tests on both EPS and PC are performed. Static and dynamic compression tests on EPS are performed as well, according to both variable- and fixed-volume methods. Falling weight tests are performed on both plane PC and sandwich PC/EPS at different energy contents to investigate possible couplings. EPS dynamic-mechanical tests are also carried out at different frequencies to evaluate temperature and strain rate influence on material stiffness. The extensive scanning electron microscopy analysis allows the investigation of strain mechanisms responsible for energy absorption as well as the validation of existing theoretical models. It is demonstrated that the energy absorption capability of these materials can be controlled at two different stages: at the macroscopic scale, by choosing the foam density able to minimise the transferred load and the acceleration value in relation to the available absorbing volume; at the microscopic scale, by modifying EPS internal structure in terms of hollow bead dimensions and walls thickness.

In patients with interstitial lung disease (ILD), the six-minute walk test (6MWT) has been rarely used, and up till now, the relationship between outcome measures of the test and baseline lung function has not yet been examined. Therefore, we assessed walk distance, oxygen desaturation, and breathlessness perception during 6MWT, and their relationships to baseline lung function in patients with ILD.Forty ILD patients with history of breathlessness during physical exertion performed a 6MWT following a standard protocol. Breathlessness perception during walk was assessed by visual analogue scale (VAS, in mm).The mean walk distance was 487 meters (range 271-689). Mean baseline oxygen saturation (Base SpO2, %) was 94% and was reduced during walk, either as mean oxygen saturation (Mean SpO2, 89%, p0.001) or as mean fall in oxygen saturation during walk (Fall SpO2, 5%). Furthermore, VAS significantly increased after walk (5 mm to 44 mm, p0.001). A close relationship of TLco and TLC to walk distance and Fall SpO2 was found (r = 0.45 and 0.42 and r = -0.75 and -0.64, respectively; p0.001, each). On the basis of regression equations by stepwise multiple regression analysis, walk distance was predicted by age and FVC (r2 = 0.50), Mean SpO2 by TLco and Base SpO2 (r2 = 0.80), and Fall SpO2 only by TLco (r2 = 0.57). Breathlessness perception was not reliably predicted by any assessed variables.We confirmed that 6MWT provides a global evaluation of sub-maximal exercise capacity in ILD patients. We also found that walk distance and oxygen desaturation, but not breathlessness perception during walk, are strictly related to baseline lung function.

Chronic obstructive pulmonary disease (COPD) is an irreversible disorder characterized by airflow obstruction and a progressive decline in forced expiratory volume in one second (FEV1). At present, no treatment except quitting smoking appears to affect the progression of the disease. Oxidative stress has been implicated in its pathogenesis. The Bronchitis Randomized on NAC Cost-Utility Study (BRONCUS) is a phase III, randomized, double-blind, placebo-controlled, parallel group, multicentre study designed to assess the effectiveness of the antioxidant agent N-acetylcysteine (NAC) in altering the decline in FEV1, exacerbation rate, and quality of life in patients with moderate to severe COPD. In addition, cost-utility of the treatment will be estimated. Patients will be followed for 3 yrs and evaluated every 3 months. The necessary sample size to demonstrate an effect on the decline in FEV1 of 20 mL x yr(-1) was estimated to be 478 patients. Five hundred and twenty-three patients with moderate to severe COPD were recruited from 10 European countries from June 1, 1997-December 31, 1999. They were 63+/-8 yrs old and consisted of 243 (46%) current smokers and 280 (54%) exsmokers. Patients had on the average 4.9+/-1.6 exacerbations during the last 2 yrs. Postbronchodilator FEVI averaged 57+/-9% and the reversibility after 400 microg of Salbutamol averaged 4+/-4% predicted. The final results of the trial will be available in about 2 yrs. The study will provide objective data on the effects of N-acetylcysteine on outcome variables in chronic obstructive pulmonary disease.

Expiratory muscle strength is a determinant of cough function. Mouth pressures during a maximal static expiratory effort (PE,max) are dependent on patient motivation and technique and low values are therefore difficult to interpret. This study hypothesized that a short, sharp and maximal expiration through a narrow aperture, a “whistle”, might provide a complementary test of expiratory muscle strength.To obtain a maximal whistle, subjects (27 healthy volunteers and 10 patients with amyotrophic lateral sclerosis) were asked to perform a short, sharp blow as hard as possible, from total lung capacity, through a reversed paediatric inhaler whistle, connected to a flange-type mouthpiece.In both healthy subjects and patients, whistle mouth pressure (Pmo,W) was closely related to the pressure measured in the oesophagus and stomach during the same manoeuvre. In healthy subjects,Pmo,WandPE,maxcorrelated with wide limits of agreement, althoughPmo,Wvalues were significantly higher thanPE,max(131±31 cmH2Oversus101±27 cmH2O, pPmo,WandPE,maxvalues were strongly related (r=0.937, pPmo,Wrepeated measurements were respectively 0.88 and 7.0%. HoweverPmo,WandPE,maxwere always smaller than the gastric pressure generated by a maximal cough.It is concluded that mouth whistle pressure, a noninvasive, reproducible and simple test, provides a reliable measure of expiratory muscle strength in healthy subjects that is acceptable to patients and can be used in a complementary fashion to maximal static expiratory effort.

Routinary evaluation of FT4 and TSH, in elderly in-patients without thyroid disease shows frequent, isolated and, often unclear, changes from normal values of plasma TSH and FT4 concentrations. A new parameter called "T index" derived from the product of FT4 and TSH values has been used by the authors. In a previous work they studied "T index" variations in 1257 elderly subjects with normal FT4 and TSH levels. They have determined the "T index" theoretic model of distribution and identified a normality range (values from 5.78 to 50.76), a suspect range (values from 2.92 to 5.78 and from 50.76 to 68.6) and a pathologic range (values less than 2.92 and more than 68.6). Aim of this study was to investigate "T index" variations in a group of 357 elderly subjects with altered FT4 and/or TSH levels.Patients were divided into eight groups according to different concentrations of FT4 and/or TSH levels. "T index" results were expressed as mean, standard deviation, maximum and minimum values. Patients were therefore divided into three groups (normality range, suspect range, pathologic range) according to "T index" distribution as previously described.In 20% of elderly people hospitalized, we found alterations of thyroid hormones levels represented mostly by: a) FT4 normal; TSH low. b) FT4 normal; TSH high, c) FT4 low; TSH normal. In case of hypothalamus-hypophysis hypothyroidism and in case of hyperthyroidism, "T index" score is, usually, less than 2.92, whereas in case of hypothalamus-hypophysis hypothyroidism and hypothyroidism "T index" score is, nearly always, more than 68.6. When TSH levels are into the range of normality "T index" score has always normality levels. The "T index" helps us to divide patients with subclinical hyperthyroidism into two groups: one with values from 5.78 to 2.92 (suspect range), and the other, with values less than 2.92 pathologic range). In patients with subclinical hypothyroidism, some patients have values from 50.76 to 68.6 (suspect range), other patients have values more than 68.6 (pathologic range).In case of subclinical hypothyroidism or subclinical hyperthyroidism the use of "T index" seems to be a good way to select the cases in which it is better to start pharmacological treatment (hormonal replacement or thyroid inhibition) from those which is better to follow-up.

Mucociliary clearance (MCC) is one of the most important nonspecific defense mechanisms of the respiratory tract, and its impairment is a well-documented feature of chronic respiratory diseases, including asthma. In vitro and in vivo data suggest that several inflammatory mediators influence the mucociliary apparatus. Epithelial damage and functional abnormalities have been described in bronchial asthma, along with changes in mucus-secreting cells and the chemical and rheological properties of airway fluid. Although the mechanisms of MCC impairment in asthma are not clearly understood, data in the recent literature suggest that airway inflammation plays a major role. In this article, we review studies on MCC alterations in light of up-to-date findings on pathogenetic mechanisms in asthma.

Airway dendritic cells are essential for stimulating naive T cells in response to inhaled antigen and for the development of allergic sensitization. IL-4 in vitro can distinguish dendritic cell lines from peripheral blood mononuclear cells. Our study had the following aims: 1) to compare the distribution of CD1a+ dendritic cells and IL-4+ cells, in the bronchial mucosa of asthmatics and controls 2) to determine the relationship between the numbers of CD1a+ dendritic cells and IL-4+ cells in the bronchial mucosa of asthmatics 3) to determine whether CD1a+ cells express the IL-4 receptor.Twenty atopic asthmatic and eight normal subjects were studied. In each subject, bronchoscopy with bronchial biopsies was performed. CD1a, IL-4, and IL-4 receptor expressions were evaluated by immunohistochemistry.The number of CD1a+ and IL-4+ cells was significantly higher in asthmatics than controls. The number of CD1a+ cells was positively correlated to the number of IL-4 + cells. Bronchial biopsy serial section studies showed that CD1a+ cells express the receptor for IL-4.These results suggest that an increased amount of IL-4 may play a physiopathologic role in maintaining the dendritic cell pool in vivo. Therefore, because of possible IL-4 activity on antigen-presenting cells in T-cell immune responses to allergens, an important new role of IL-4 in asthma inflammation can be envisaged.

We evaluated the outcome of the spirometry quality control program of the SA.R.A. multicenter project, the aim of which is the multidimensional assessment of asthma and COPD in the elderly (/= 65 yr). The factors determining this quality were also evaluated. The program was based on standardized procedures (ATS recommendations), performed by specifically trained and certified personnel; a fully-computerized spirometer with customized software was used for spirometry. A reference center made monthly controls. Overall, 638 cases and 984 controls were examined. Spirometric measurements were obtained in 607 cases and 912 controls; 508 and 747 tests with at least three acceptable curves were obtained in cases and in controls, respectively (NS). The percentage of reproducible tests ranged between 95.8% for FEV(1) in controls and 87.6% for FVC in cases. The average reproducibility for FEV(1) was 61.6 ml in cases and 58.3 ml in controls (NS). Cognitive impairment, shorter 6-min walk distance, and lower educational level were found to be independent risk factors for a poorer acceptability rate (logistic regression analysis). Male sex and age were risk factors for a poorer reproducibility of FEV(1). Reproducibility tended to improve with time (p0.001). Although spirometry becomes increasingly difficult in aging patients, a rigorous quality control program can ensure that reliable data are obtained in the majority of patients.

Sarcoidosis is characterized by a diffuse alveolar inflammatory process, although bronchial airways are often involved. This study compares the cellular profiles of induced sputum (IS), bronchial washing (BW), and BAL in newly diagnosed sarcoidosis patients to those in control subjects, and examines whether inflammatory cell counts from IS are correlated with inflammatory cell counts from BW and BAL in sarcoidosis patients.We recruited 15 untreated patients with stage I and II pulmonary sarcoidosis and 12 healthy volunteers. Sputum was induced with hypertonic saline solution in all individuals. Bronchoscopy was performed on a different occasion in all patients and in five control subjects.Mean lymphocyte counts in IS, BW, and BAL fluid from sarcoidosis patients were significantly higher than in control subjects (9.4% vs 3.8%, p0.05; 12.6% vs 3.9%, p0.05; 24.1% vs 2.6%, p0.05, respectively). Moreover, total cell count and percentage of epithelial cells in IS were significantly higher in sarcoidosis patients than in control subjects (p0.01 and p0.05, respectively). In sarcoidosis patients, comparison between different samples showed significantly higher percentages of macrophages in BW and BAL than in IS (p0.05 and p0.01, respectively), whereas the percentage of neutrophils was higher in IS compared with BW and BAL (p0.01 and p0.001, respectively). Finally, the percentage of lymphocytes in IS was significantly lower than that in BAL (p0.05) but not that in BW.We demonstrated that, compared with IS in healthy control subjects, IS in untreated pulmonary sarcoidosis patients contains more total cells, lymphocytes, and epithelial cells. Although the relative proportion of inflammatory cells in the three samples differed, lymphocyte counts in IS were high. This finding suggests that IS could be used as a valuable alternative to more conventional invasive techniques in clinical assessment of pulmonary sarcoidosis patients.

In chronic obstructive pulmonary disease (COPD), mucus hypersecretion is considered one of the main symptoms. Recently the natural history of COPD has been better defined and chronic mucus hypersecretion is now viewed as linked to the acceleration of forced expiratory volume in one second (FEV1) decline and not merely as an "innocent disorder". In the past, mucoactive drugs were claimed to treat mucus hypersecretion. However, since most mucoactive drugs have not been evaluated in large clinical studies, European Respiratory Society and American Thoracic Society COPD guidelines discourage their use for treatment of COPD patients. Clinical trials have been often disappointing because improvement in lung function has been adopted as the main outcome, despite bronchial obstruction in COPD patients being frequently irreversible or poorly reversible. Thus, goals for treatment in COPD patients should include not only improvement in lung function, but also clinical symptoms and quality of life. Moreover, to rightly allocate these drugs in COPD management and to try to modify the natural history and progression of COPD, mucus hypersecretion might require treatment in the first stage of the disease. In conclusion, mucoactive treatments for chronic obstructive pulmonary disease patients should be re-evaluated in the future in patients selected according to demographic factors such as degree and reversibility of bronchial obstruction due to mucus hypersecretion, patient smoking habits and other socioeconomic parameters which have proved to be relevant to the progression of the disease, according to the latest recommendations for guidelines on clinical trials of mucoactive drugs in chronic bronchitis and chronic obstructive pulmonary disease.

Gastroesophageal reflux (GER) is an abnormal condition which causes the gastrointestinal contents to return to the esophagus, owing to alterations in the mechanisms which control gastroesophageal continence function [1].