The Global Usability Score Short-Form for the simplified assessment of dry powder inhalers (DPIs) usability.

BACKGROUND: The choice of the Dry Powder Inhaler (DPI) to prescribe is a critical issue. The estimation of DPIs usability depends on the objective assessment of several indices related to both subjective and objective determinants. The Global Usability Score (GUS) Questionnaire is a comprehensive tool usable for checking, comparing, and ranking inhalers' usability objectively in real life, but it takes some time to fill. AIM: The aim of this study was to favour the quicker check of DPIs usability in clinical practice by means of a simplified short-form GUS (S-GUS) Questionnaire, while maintaining the high specificity and sensitivity of the original, extended version of the Questionnaire (O-GUS questionnaire). METHODS: The usability of the six most prescribed DPIs was assessed in 222 patients with persistent airway obstruction and needing long-term inhalation treatments. LASSO regression and multicollinearity test were used to select the subset of questions of the O-GUS questionnaire, with the highest information power. Each item was then scored using the corresponding coefficient in the linear regression (normalized at 50 as the O-GUS score). Agreement between the original and the short-form questionnaire was evaluated using the Cohen's kappa statistic (κ). The overall S-GUS values obtained for each DPI were then compared to those from the O-GUS, in the same patients, using a Bayesian indirect comparison (IC) model. RESULTS: After the statistical selection of the items mostly contributing to the overall score, the novel S-GUS questionnaire consists of twelve items only. Nine items are related to patients' opinion before DPIs handling, and three to the nurse's assessment after DPIs practicality. O-GUS and S-GUS score were strongly correlated (R2=0.9843, p<0.0001) and the usability score calculated for each DPI by means of the O- and of S- GUS overlapped almost completely (κ=84.5%, 95% CI 81.3% to 89.2%). Furthermore, S-GUS was much faster to complete than O-GUS (mean time 6.1 vs 23.4 minutes, p<0.001). Estimates of S-GUS, obtained from the IC model, allowed to propose a simple classification of usability: "good" by GUS values >25; "pretty good" by values ≤25≥15, and "insufficient" by values <15. CONCLUSIONS: The S-GUS proves as much specific and suitable as the extended O-GUS questionnaire in measuring DPIs usability, while maintaining the same high sensitivity. As the time required for its use is quite shorter, S-GUS is also particularly suitable and helpful in current clinical practice.

Fluticasone furoate/vilanterol 92/22 µg once a day: a 12-month study on outcomes in mild to moderate asthma.

BACKGROUND: Fluticasone furoate/vilanterol (FF/V) is an effective long-acting ß2 agonist/inhaled corticosteroid combination for managing persistent bronchial asthma. The aim of the study was to assess the outcomes achievable in patients with mild to moderate asthma receiving FF/V 92/22 µg once daily for 12 months. METHODS: Data were automatically and anonymously obtained from the institutional database: forced expiratory volume in 1 s predicted values; the exacerbation and hospitalization rates; days of hospitalization; general practitioner (GP) or specialist visits; days of inactivity; courses of systemic steroids or antibiotics were recorded at baseline and after 3, 6 and 12 months of treatment. The overall adherence to treatment was also calculated. Analysis of variance was used for checking the trends of variables. The improvement in lung function was significant ( p < 0.001) and time dependent. The mean (±standard error) exacerbation rate per patient changed from 1.05 (±0.16) at baseline to 0.28 (±0.07) after 3 months, 0.33 (±0.08) after 6 months and 0.18 (±0.08) after 12 months ( p < 0.001). The mean hospitalization rate per patient changed from 0.30 (±0.07) at baseline to 0.08 (±0.04) after 3 months, 0.10 (±0.05) after 6 months and 0.03 (±0.03) after 12 months ( p < 0.001). Also mean duration of hospitalization and days of inactivity were reduced over time ( p < 0.001). GP visits were also reduced, together with specialist visits (both p < 0.001). Steroid and antibiotic courses dropped significantly ( p < 0.001 and p < 0.001, respectively). Moreover, changes in all outcomes considered proved time dependent, particularly over the second semester. Finally, over time, adherence to treatment was high. CONCLUSIONS: The once-daily inhalation of combined FF/V 92/22 µg optimized systematically the exacerbation and hospitalization rates in mild to moderate asthma, together with all other outcomes over time. The effectiveness of FF/V 92/22 µg once daily proved to be time dependent over the period of the study.

Correction to: Fluticasone furoate/Vilanterol 92/22 µg once-a-day vs Beclomethasone dipropionate/Formoterol 100/6 µg b.I.D.: a 12-month comparison of outcomes in mild-to-moderate asthma.

[This corrects the article DOI: 10.1186/s40248-018-0131-x.].

Fluticasone furoate/Vilanterol 92/22 µg once-a-day vs Beclomethasone dipropionate/Formoterol 100/6 µg b.I.D.: a 12-month comparison of outcomes in mild-to-moderate asthma.

BACKGROUND: Bronchial asthma is an inflammatory disease of the airways. Beclomethasone dipropionate/Formoterol (BDP/F) and Fluticasone furoate/Vilanterol (FF/V) are two of the most effective LABA/ICS combinations for managing persistent bronchial asthma. Aim of the study was to compare the outcomes achieved in mild-to-moderate asthma patients assuming BDP/F 100/6 µg b.i.d. (Group A) or FF/V 92/22 µg once-daily (Group B) for 12-months. No head-to-head long-term comparison is available at present. METHODS: Data were automatically and anonymously obtained from the institutional database: FEV1% predicted values; the exacerbation and hospitalization rates; days of hospitalization; GP and/or specialist visits; days of inactivity; courses of systemic steroids and/or antibiotics were recorded at baseline and after 3, 6 and 12 months of both treatments. The overall adherence to treatments was also calculated. The propensity score method was used for matching and comparing the two cohorts of patients; Anova and Wilcoxon tests were used for checking the trends and time-to-time comparisons over the period; statistical significance was accepted for p < 0.05. RESULTS: The PS-matching process returned a cohort of 40 group A patients matched with 40 patients of group B, fully comparable for demographics, clinical characteristics, and comorbidities. The improvement in lung function was significant in both groups (p < 0.001), even if it was significantly higher and time-dependent in group B. The mean (±SE) exacerbation rate/patient changed from 0.63 (±0.13) at baseline to 0.53 (±0.12) after three; to 0.58 (±0.13) after six, and to 0.60 (±0.18) after twelve months in group A (p = ns), while from of 1.05 (±0.16) at baseline, to 0.28 (±0.07) after three; to 0.33 (±0.08) after six, and to 0.18 (±0.08) after twelve months in group B (p < 0.001), respectively. The mean hospitalization rate/patient changed from 0.25 ± 0.07 at baseline to 0.15 (±0.06) after three; to 0.08 (±0.04) after six, and to 0.13 (±0.05) after twelve months in group A (p = ns), while from 0.30 (±0.07) at baseline to 0.08 (±0.04) after three; to 0.10 (±0.05) after six, and to 0.03 (±0.03) after twelve months in group B (p < 0.001), respectively. Also mean duration of hospitalization and days of inactivity were in favour of FF/V treatment over time (in both cases p < 0.001). GP's visits were reduced by both treatments (p < 0.007 in group A and p < 0.001 in group B, respectively, while Specialist's visits only dropped during FF/V (p < 0.001). Steroid and antibiotic courses were significantly reduced by both treatments, even if more systematically in group B (p < 0.001 vs p < 0.007, and p < 0.001 vs p < 0.044, respectively). Moreover, changes in all outcomes considered proved time-dependent during the FF/V treatment only, particularly over the second semester. Finally, the overtime adherence to treatment was higher by 22 days during FF/V . CONCLUSIONS: Both the ICS/LABA combinations proved effective, even if characterized by different patterns of effectiveness either in terms of lung function and of long-term clinical outcomes. Only the once-daily inhalation of combined FF/V 92/22 µg once-daily optimized systematically the exacerbation and hospitalization rates in mild-to-moderate asthma, together with all other outcomes over time. The effectiveness of FF/V 92/22 once-daily µg proved progressive and time-dependent over the twelve-month period of the study, and associated to a higher adherence to treatment.

Instant velocity and consistency of emitted cloud change by the different levels of canister filling with Metered Dose Inhalers (MDIs), but not with Soft Mist Inhalers (SMIs): a bench study.

BACKGROUND: Inhalation is the preferred route for respiratory drug delivery, but several factors contribute to the variability of the respirable dose fraction. Instant velocity and the dynamic characteristics of the droplet cloud represent crucial factors. Aim was to measure and compare the instant velocity and the consistency of emitted cloud from five different MDIs (A - Salbutamol sulphate 100mcg, GSK; B - Salbutamol sulphate 100mcg, Valeas; C - Salmeterol xinafoate/Fluticasone propionate 25/125mcg, GSK; D - Formoterol fumarate/Bechlomethasone propionate 6/100mcg, Chiesi; E - Formoterol fumarate/Fluticasone dipropionate 5/125mcg, Mundipharma) and one SMI (Tiotropium bromide 5mcg, Boehringer Ingelheim), at different distance from the nozzle and canister filling. METHODS: Measurements were made at 90, 50, and 10% of canister filling, and at 5, 10, and 20 cm from the nozzle, for a total of 972 puffs. A high speed video photography protocol was adopted and high speed cameras (1.200 frames/sec.) were used. Data were acquired by means of specialized softwares. Temperature, humidity, and vibrations occurrence were strictly controlled during measurements. Statistics: Anova and p < 0.05 were accepted as the minimum significance level. RESULTS: MDIs generated different Instant velocities: MDI B generated the highest, while MDI A the lowest. As expected, velocity decreased in proportion to the distance from the nozzle. Except with MDI C, instant velocity decreased significantly over the first 50% of canister emptying, but dropped by >33% at 90% of emptying with all other MDIs (p < 0-037; p < 0.001; p < 0.005, and p < 0.001, respectively). Instant velocity was extremely lower (p < 0.001) and constant for all levels of canister filling (p = ns) with SMI. All MDIs had a very fast jet phase, ranging 0.01-0.03 s at 10 cm, and 0.03-0.05 s at 20 cm from the nozzle, without any significant difference from each other (p = ns). MDIs generated a cloud similarly tight (p = ns) at 10 and 20 cm from the nozzle, while it was extremely wider and constant with the SMI (p = 0-001). Also the cloud turbulence was minimized during the SMI emission. DISCUSSION AND CONCLUSIONS: MDIs are characterized by a substantial variability in both their instant velocity and consistency of the emitted cloud at different levels of canister filling. SMI generates a much slower soft mist cloud which is constantly homogeneous and independent of canister emptying. These peculiarities assessed at bench are suggesting a higher dose consistency and a much more effective therapeutic performance also in real life.

Cost of persistent asthma in Italy.

BACKGROUND: Asthma is a common disease of the airways with a significant burden for the society and for patients' quality of life. The Social Impact of Respiratory Integrated Outcomes (SIRIO) study estimated a mean cost of 1,177.40 € per patient/year in Italy, in 2007. The aim of the present study was to update the cost of persistent asthma patients in Italy. METHODS: An observational, retrospective, bottom-up analysis was carried out starting from the data base operating in the Lung Unit of the Specialist Medical Centre (CEMS), Verona (Italy), over the period June 2013-December 2015. Patients' data were recorded over the 12 ± 2 months before the enrollment and during 12 ± 2 months of follow-up. The prospective was the Italian National Health Service and the broad Italian society. Clinical data were measured in terms of forced expiratory volume in 1 s (FEV1%) and number of relapses. Healthcare resources (namely; number of hospitalizations and/or ER admissions; number of visits; drug use and duration, and indirect costs) were recorded. RESULTS: The cohort consisted of 817 patients with persistent asthma of different severity. They had a 42.96% male prevalence; a mean (±SE) age of 49.06 (±0.64) years; a mean 87.47% (±0.81) FEV1% pred. in baseline, and 69.16% of subjects had comorbidities. The mean (±SE) number of relapses was 0.91 (±0.09) per patient/year before the enrolment. After 12 months, FEV1% significantly improved by +6.31% (±0.45) from the corresponding baseline value (p < 0.001). The number of relapses decreased of -0.46 (±0.09) (p < 0.001). The estimated total annual cost per asthmatic patient was 1,183.14 € (±65.79 €) during the 12 months before the enrolment, and 1,290.89 € (±68.74 €) throughout the follow-up. The increase was mostly due to the significantly increased duration of therapeutic strategies. The costs of hospitalization, general practitioner and rescue medications were significantly decreased. CONCLUSIONS: The periodic update of cost analysis is a key to monitor the trend of main asthma outcomes and related expenditure over time. It allows to plan the most convenient actions in terms of prevention strategies and effective interventions, with the aim of optimizing the healthcare resources consumption and maximizing the impact on clinical outcomes and patients' quality of life. The role of an appropriate pharmacological strategy still proves crucial in minimizing asthma morbidity and the corresponding socio-economic impact.

Fluticasone furoate/Vilanterol 92/22 µg once-a-day vs Beclomethasone dipropionate/ Formoterol 100/6 µg b.i.d.: a 12-week cost analysis in mild-to-moderate asthma.

BACKGROUND: Asthma is a disease with high cost for the National Health Service. Two of the most recent LABA/ICS combinations for persistent bronchial asthma are Beclomethasone dipropionate/Formoterol (B/F) delivered via the Nexthaler device and Fluticasone furoate/Vilanterol (F/V) delivered via the Ellipta device. No comparison has been carried out yet in terms of cost analysis in asthma, to our knowledge. Aim of the present monocentric, observational, retrospective study was to calculate and compare the costs of mild-to-moderate asthma patients assuming B/F 100/6 µg b.i.d. to those of patients assuming F/V 92/22 µg once-a-day over a 12-week treatment period from the Italian National Health Service perspective. METHODS: Data were obtained automatically and anonymously from the institutional database of the Lung Unit of the Specialist Medical Centre (CEMS), Verona, Italy, UNI EN ISO 9001-2008 validated. FEV1 values, number of relapses, healthcare resources as hospitalizations due to asthma relapses, days of hospitalization, general practitioner (GP), specialist visits, and days of inactivity, were recorded over the study period together with the use of extra medications (systemic steroids and antibiotics). In order to compare the outcomes achieved in both groups, the propensity score matching method was used in STATA, and statistical significance was accepted for p < 0.05. RESULTS: Clinical data of 77 patients treated with B/F b.i.d (Group A) and of 40 patients treated with F/V 92/22 µg once-a-day (Group B) were selected. The PS-matching process, designed as matching on the baseline covariates, gender, age, FEV1 and comorbidities, returned a cohort of 40 group A patients of the entire cohort matched with 40 patients of group B, fully comparable for demographics and clinical characteristics. In the PS-matched cohort, the mean (±SE) number of relapses per patient during the follow-up was 0.53 (±0.12) in group A and 0.28 (±0.07) in group B. In group A, n = 25 (62.50 %), n = 9 (22.50 %), and n = 6 (15 %) patients had 0, 1, 2 relapses, respectively. In group B, n = 29 (72.50 %), and n = 11 (27.50 %) had 0 and 1 relapse, respectively. Over the study period, the average number of hospitalizations per patient was 0.15 (±0.06), with 0.28 (±0.12) days of hospitalization in group A, and 0.08 (±0.04) with 0.08 (±0.04) days of hospitalization in group B, respectively. The difference between the two groups in terms of FEV1(L) improvement vs baseline was 0.11 in favour of group B (p = 0.007). When results were compared, the improvement in lung function obtained in group B proved significantly higher both in terms of absolute FEV1 and of FEV1 % predicted. The mean (±SE) cost of hospitalizations per patient was € 345.30 (±133.23) in group A and € 172.65 (±98.18) in group B, respectively, with a mean not significant difference of - € 172.65 in favour of group B (p = 0.9). In particular, the mean (±SE) cost for visits per patient was € 26.82 (±3.73) in group A and € 11.36 (±2.30) in group B (p = 0.002), and the mean cost for rescue medications per patient was € 35.24 (±6.93) in group A, and € 18.73 (±3.38) in group B, respectively (p = 0.05). CONCLUSIONS: Even if both ICS/LABA combinations were checked over a limited period of time, they seem characterized by a different profile in terms of effect on lung function and economic impact on mild-to-moderate asthma. The once-daily inhalation of combined Fluticasone furoate/Vilanterol 92/22 µg showed the potential for enhanced clinical outcomes and reduced costs when compared to Beclomethasone dipropionate/Formoterol 100/6 µg b.i.d.

Cognitive dysfunction in severe chronic obstructive pulmonary disease (COPD) with or without Long-Term Oxygen Therapy (LTOT).

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory condition which can lead to comorbidities of variable severity, cognitive dysfunction included. The role of supplemental oxygen in preventing COPD-induced cognitive deterioration is still debated, but only episodically investigated. The aim of this study was to compare the cognitive pattern of hypoxemic COPD subjects treated with long-term oxygen (LTOT) to that of patients of comparable severity assuming oxygen on irregular basis, and to normal reference values. METHODS: Lung function, arterial blood gases, health status, and cognitive function measured by means of four psychometric tests focusing different domains of cognition (such as: MMSE, Clock test; TMT-A; TMT-B) were assessed in 146 well matched hypoxemic COPD patients (males n = 96, 66%; mean age = 70.5 ± 12.9). Seventy-three patients were assuming long-term oxygen (LTOT), while the remaining seventy-three were only using oxygen as needed (AN). Regarding statistics, t test and ANOVA (Duncan test) were used to analyze data, assuming a p < 0.05 as the lowest limit of significance. RESULTS: Even though all COPD patients showed a poorer psychometric profile vs corresponding normal reference values, LTOT patients showed a lower prevalence of severe deterioration in cognition. Also the extent of impairment was significantly lower in these patients when assessed by TMT-A and TMT-B (p < 0.012 and 0.001, respectively), but not when measured by MMSE and Clock test (both p = ns). Several domains of cognition are variably affected by persistent hypoxemia in COPD patients. A panel of psychometric tools is needed for identifying the pattern of cognitive dysfunctions in these patients. Memory and attention (functions assessed by MMSE and Clock test) are only mildly-moderately affected, while visual processing, reproduction of numeric sequences, cognition flexibility, and shifting capacity (functions assessed by TMT-A and TMT-B) are much more deteriorated (p < 0.012 and p < 0.001, respectively). CONCLUSIONS: Only LTOT allows to preserve significantly (p < 0.022) cognitive functions from the COPD-induced deterioration. This assumption is of strategic value for COPD patients who are prescribed long-term oxygen because they frequently are not aware of the cognitive risks related to their condition.

Costs of illness analysis in Italian patients with chronic obstructive pulmonary disease (COPD): an update.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide, and its epidemiological, clinical, and socioeconomic impact is progressively increasing. A first estimate of the economic burden of COPD in Italy was conducted in 2008 (the SIRIO [Social Impact of Respiratory Integrated Outcomes] study). The aim of the present study is to provide an updated picture of the COPD economic burden in Italy. METHODS: Sequential patients presenting at the specialist center for the first time during the period 2008-2012 and with record file complete (demographic, clinical, lung function, and therapeutic data; health care resources consumed in the 12 months before the enrollment and for the 3 subsequent years) were selected from the institutional database. RESULTS: Two hundred and seventy-five COPD patients fitting the inclusion criteria were selected (226 males; mean age: 70.9 years [standard deviation: ±8.4 years]; 45.8% were from the north, 25.1% from central Italy, and 29.1% from south Italy). COPD-related average costs per patient in the 12 months before enrollment were as follows: hospitalization: €1,970; outpatient care: €463; pharmaceutical: €499; and indirect costs: €358. Average direct costs and total societal costs were €2,932 and €3,291, respectively. Direct cost was €2,461 (hospitalization: €1,570; outpatient: €344; and pharmaceutical: €547) in the first year of follow-up, while total societal cost was €2,707. No significant difference was reported in any cost category between sexes. CONCLUSION: The therapeutic approach followed in a specialist center, based on the application of clinical guidelines, has been shown to be a highly effective investment for the long-term management of COPD. A small increase of pharmaceutical costs per year allowed a substantial saving in terms of hospitalizations, costs related to outpatient services, and indirect costs.

Extent and prevalence of cognitive dysfunction in chronic obstructive pulmonary disease, chronic non-obstructive bronchitis, and in asymptomatic smokers, compared to normal reference values.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) can affect cognition. The effects of other less severe chronic airway disorders on cognition remain to be clarified. This study aimed to measure and compare cognitive deterioration in subjects with COPD, subjects with chronic non-obstructive bronchitis (CNOB), and asymptomatic smokers (AS), and to relate the corresponding prevalence to several demographic and clinical variables and to normal reference values. METHODS: Four hundred and two subjects (COPD n=229, CNOB n=127, and AS n=46) of comparable age were included in the study. Cognitive impairment was assessed using the Mini Mental Status test, the Clock Drawing test, and the Trail Making test A and B. RESULTS: The extent and prevalence of cognitive deterioration was greater in COPD subjects, followed by CNOB subjects and AS (P<0.001). The Medical Research Council and COPD Assessment test scores, forced expiratory volume in the first second predicted, and arterial partial pressure of O2 and of CO2 were related to the extent and the prevalence of cognitive deterioration. COPD subjects, CNOB subjects, and AS aged 40-69 years showed the greatest cognitive impairment (P<0.01 compared to normal values). This was particularly clear in COPD subjects. CONCLUSION: Cognitive impairment may start at the early stages of chronic airway damage and progress with a worsening of the respiratory condition. Indeed, the greatest cognitive deterioration was seen in COPD subjects. Cognition impairment may contribute to explaining the insufficient adherence to therapeutic plans and strategies, and the increasing social costs in respiratory subjects.

Sensitivity of the COPD assessment test (CAT questionnaire) investigated in a population of 681 consecutive patients referring to a lung clinic: the first Italian specific study.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality at global level even if still underestimated. The insufficient use of specific tools for an objective definition and staging, the inadequate awareness of COPD, but also a difficult patient-to-doctor communication, can contribute to the poor management of COPD. A very simple, short and sensitive questionnaire (the "COPD Assessment Test" - CAT questionnaire) is now available for assessing the impact of COPD on the patient's health. The present study was designed to provide such evidence using data generated throughout Italy. METHODS: The Italian validated version of the CAT questionnaire was distributed to 681 consecutive COPD patients of different severity (males = 480), well matched for age, gender, smoking habit, geographical distribution, BMI, dyspnoea score and educational level. The CAT score variability was investigated vs all anagraphic, and clinical variables, and spirometric indices of lung function (regression). No Italian data are available to our knowledge on the CAT use, neither in General Medicine, nor in the specialist setting. RESULTS: Data of this study confirmed that the CAT questionnaire is a sensitive, simple, and quick tool for assessing the respiratory status of COPD patients. The CAT score proved not conditioned by the patient's age, gender, body size, geographical origin, and educational level. It was inversely correlated with the spirometric values, even if not uniquely linked to them. CONCLUSIONS: The CAT score does not represent a surrogate measurement of lung function: it is an instrument which focuses on different areas of respiratory health in COPD patients, thus providing an useful and objective tool for the long-term clinical and therapeutic monitoring of COPD patients in the specialist outpatient setting.

Changes in blood hemoglobin and blood gases PaO2 and PaCO2 in severe COPD overa three-year telemonitored program of long-term oxygen treatment.

BACKGROUND: Information on the effects of long-term oxygen treatment (LTOT) on blood hemoglobin (Hb) in severe COPD are limited. The aim was to assess blood Hb values in severe COPD, and investigate the time-course of both Hb and blood gas changes during a 3-year telemetric LTOT. METHODS: A cohort of 132 severe COPD patients (94 males; 71.4 years ± 8.8 sd), newly admitted to the tele-LTOT program, was investigated. Subjects were divided according to their original blood Hb: group A: <13 g/dL; group B: ≥13 < 15 g/dL; group C: ≥ 5 < 16 g/dL; group D: ≥16 g/dL. Blood Hb (g/dL), PaO2 and PaCO2 (mmHg), SaO2 (%), and BMI were measured at LTOT admission (t0), and at least quarterly over three years (t1-t3). Wilcoxon test was used to compare t0 vs. t1 values; linear regression to assess a possible Hb-BMI relationship; ANOVA to compare changes in Hb time-courses over the 3 years. RESULTS: LTOT induced a systematic increase of PaO2, and changes were significant since the first year (from 52.1 mmHg ± 6.6sd to 65.1 mmHg ± 8.7 sd, p < 0.001). Changes in SaO2 were quite similar. Comparable and equally significant trends were seen in all subgroups (p < 0.001). PaCO2 dropped within the first year of LTOT (from 49.4 mmHg ± 9.1sd to 45.9 mmHg ±7.5 sd, p < 0.001): the t0-t1 comparison proved significant (p < 0.01) only in subgroups with the highest basal Hb, who showed a further PaCO2 decline over the remaining two years (p < 0.001). Hb tended to normalization during LTOT only in subgroups with basal Hb > 15 g/dl (ANOVA p < 0.001); anemic subjects (Hb < 13 g/dl) ameliorated not significantly in the same period (ANOVA = 0.5). Survival was independent of the original blood Hb. Anemia and polyglobulia are differently prevalent in COPD, the latter being the most represented in our cohort. LTOT affected both conditions, but to a different extent and according to different time-courses. The most striking Hb improvement was in polyglobulic patients in whom also PaO2, PaCO2 and SaO2 dramatically improved. In anemic subjects effects were smaller and slower, oxygenation being equally ameliorated by LTOT. CONCLUSIONS: LTOT effects on Hb and PaCO2 are regulated by an Hb-dependent gradient which seems independent of the original impairment of blood gases and of effects on oxygenation.

The impact of LABA+ICS fixed combinations on morbidity and economic burden of COPD in Italy: a six-year observational study.

BACKGROUND: In Italy, chronic obstructive pulmonary disease (COPD) has progressively received increasing attention in the last decade, and its impact has been investigated extensively in both clinical and pharmacoeconomic terms. METHODS: In 2004, the national health authorities stated the appropriateness of long-acting ß(2) agonists (LABA) and inhaled corticosteroids (ICS) fixed combinations for treating COPD, even though this pharmaceutical option was limited to the severe and very severe stages of the disease (forced expiratory volume in one second [FEV(1)] <50% predicted). The effectiveness in primary care of this official recommendation has been investigated in 1125 COPD patients together with the appropriateness of the therapeutic approach to the disease. RESULTS: and conclusions: Clinical and economic outcomes were monitored over the 3 years before (2001-2003) and the 3 years following this recommendation (2004-2006), and statistically compared (t-test). In general, the overall impact of COPD changed progressively after the pronunciation of the public health authorities. In particular, since the point when LABA/ICS fixed combinations were officially recommended, both morbidity of COPD and the corresponding consumption of healthcare resources have progressively lowered. Moreover, the appropriateness of the pharmaceutical approach increased in the same period, thus emphasizing the importance of the optimization of therapeutic strategies in reducing the long-term impact of the disease.

Clinical and pharmacoeconomic profile of COPD patients with FEV1 50--60% predicted: pilot study on the impact of the extended indication of ICS/LABA.

BACKGROUND: The use of inhaled corticosteroids (ICS) and long-acting beta(2) adrenergics (LABA) in fixed combination (ICS/LABA) was recently extended to COPD patients with a baseline FEV(1) 50-60% predicted, thus broadening the original guideline indications (GOLD 2006) that limited their use only to stages III and IV. METHOD: The present study was carried out to assess the clinical profile of this new subset of patients, with a view to providing data for future studies on the impact of this novel extension of ICS/LABA use in COPD. RESULTS: Data from the present observational cross-sectional study suggest that COPD patients with FEV(1) 50-60% predicted depict a dichotomic condition: actually, even though resembling milder patients in terms of frequency and severity of their respiratory symptoms, they are much more similar to severer patients in terms of rate of hospital admissions and resource consumption (p50.01). In other words, this subset of patients seems to represent a peculiar condition in the evolutional phase of COPD during which therapeutic treatment should be intensified in order to slow down the disease progression effectively. Nevertheless, independently of the severity, the general therapeutic approach to COPD was found to be greatly inadequate when compared to GOLD guidelines, particularly in terms of appropriateness. CONCLUSIONS: These findings should pave the way for future studies aimed to long-term monitoring of main outcomes and to evaluate the overall impact of earlier ICS/LABA use on disease progression and lung function decline in COPD.

Cost analysis of GER-induced asthma: a controlled study vs. atopic asthma of comparable severity.

Bronchial asthma is a costly disease: while the role of pharmaceutical strategies was greatly emphasised in order to alleviate its economic burden, the aetiological approach to asthma has received much less attention from this point of view. The impact of gastro-oesophageal reflux (GER)-related asthma was assessed in comparison to atopic asthma in 262 matched patients, and the corresponding direct and indirect annual costs calculated. All subjects were screened by means of a 95-item self-questionnaire. The overall resource utilisation was calculated for the last 12 months. Drug-induced annual costs were euro 290.4 (interquartile range-iqr 32.8) in atopic and euro 438.4 (iqr 27.8) in GER-related asthma (p<0.001); expenditure for medical consultations and diagnostics were euro 166.1 (iqr 14.8) vs. euro 71.6 (iqr 11.0) (p<0.001), and euro 338.4 (20.0) vs. 186.9 (iqr 26.5) (p<0.001), respectively. Direct costs due to hospital admissions and indirect costs due to absenteeism were also higher in GER-related asthmatics: 2.201.7+/-90.0 vs. euro 567.1+/-11.0 (p<0.001), and euro 748.7+/-94.7 vs. euro 103.6+/-33.9 (p<0.001), respectively. The total annual cost per patient was euro 1246.7 (iqr 1979.6) in atopic and euro 3967.1 (iqr 3751.5) in GER-related asthma, p<0.001. In conclusion, GER-induced asthma has a more relevant economic impact on healthcare resources than atopic asthma. Although further studies are needed, present data tend to demonstrate that when facing difficult asthma (GER-related asthma in this case), the aetiological assessment of the disease plays a critical role in optimising the approach to patients' needs.