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BACKGROUND: The Vibralung Acoustical Percussor is a new airway clearance therapy (ACT) utilizing intrapulmonary sound waves in addition to positive expiratory pressure (PEP). We evaluated the safety of the Vibralung and collected preliminary data on its ability to mediate sputum expectoration in individuals with cystic fibrosis (CF). METHODS: Over two separate studies, 10 and 11 mild to moderate CF patients were recruited for study I and II, respectively. Study I: Vibralung was used for 20 min with either no sound (NS: PEP only) or sound (S: PEP and sound) on randomized visits. Pulmonary function, diffusion capacity of the lungs for carbon monoxide and nitric oxide (DLCO/DLNO), symptoms, and peripheral oxygen saturation (SpO2) were measured at baseline and at 1 and 4 h post treatment. Expectorated sputum was collected over 4 h post treatment. Study II: over 5 days of in-hospital therapy, the Vibralung or vibratory vest therapy (Vest) were used for two therapy sessions per day, with sputum collected for 20 min following each therapy and pulmonary function accessed pre and post each 5-day period (days 1-5 or 7-11) in a randomized crossover design. RESULTS: Vibralung usage resulted in no change from baseline to 4 h post in pulmonary function, SpO2 or symptoms ( p > 0.05). At 4 h post therapy, the DLCO- and DLNO-derived measure of alveolar-capillary unit function (DM/ VC) showed improvement (DM/ VC = 12.5 ± 5.5 versus 7.3 ± 18.8% change, S versus NS) with no difference between S and NS ( p = 0.74). Sputum expectoration was similar between S and NS conditions (wet sputum = 10.5 ± 4.6 versus 9.9 ± 3.2 g, S versus NS, p = 0.25). There were no differences in the improvement in pulmonary function between Vibralung and Vest during either 5-day period during the hospital stay. CONCLUSIONS: Vibralung was well tolerated and caused no detrimental changes in pulmonary function metrics. The Vibralung appears to be a safe ACT in individuals with CF.

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We conducted a retrospective study in a general hospital in Buenos Aires, Argentina (2009-2015) aimed at evaluating outcomes in HIV-infected pregnant women (HIPW), who were prescribed raltegravir (RAL)-containing antiretroviral therapy (ART). A total of 239 HIPW were enrolled in our study; among them 31 received RAL (12.9%) at different clinical stages: i) intensification (INS): addition of RAL to current ART because of detectable antepartum viral load, 13 (41.9%); ii) late presenter (LP): standard ART + RAL as fourth drug, 15 (48.4%); iii) treatment of resistant-HIV: 3 (9.7%). Median gestational age at RAL initiation was 34 weeks and median exposure was 30 days. In INS-group, median viral load (VL) decrease was 1.48 log10. In LP-group, median VL decline was 2.15 log10. No clinical adverse events or maternal intolerance attributable to RAL were observed. Elective cesarean section was done in 51.7%; mild elevation of transaminases was observed in 35% of neonates. No vertical transmission was documented.

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RATIONALE: Despite the demonstrated advantageous systemic changes in response to regular exercise for individuals with cystic fibrosis (CF), exercise is still viewed as an elective rather than a vital component of therapy, and it is likely that these benefits extend to and are partially mediated by exercise-induced changes in ion regulation. OBJECTIVE: We sought to determine if exercise could provide comparable improvements in ion regulation in the CF lung as albuterol, measured using exhaled breath condensate (EBC) collection and nasal potential difference (NPD). METHODS: Fourteen CF (13-42 yrs.) and sixteen healthy (18-42 yrs.) subjects completed a randomized crossover study of albuterol and submaximal exercise. EBC was collected at baseline, 30- and 60-min post-albuterol administration, and at baseline and during three separate 15 min cycling exercise bouts at low, moderate, and vigorous intensity (25, 50 and 65% of the maximum workload, respectively). NPD was performed at 30- and 80-min post albuterol or following moderate and vigorous intensity exercise. RESULTS: CF subjects had lower EBC Cl(-), but no difference in EBC Na(+) at baseline when compared to healthy subjects. EBC Cl(-) increased four-fold with moderate exercise which was similar to that seen 60-min post albuterol administration for CF subjects. Neither exercise nor albuterol altered EBC Na(+). The change in NPD voltage with amiloride (ΔAmil) was greater and there was minimal Cl(-) secretion (ΔTCC) seen at baseline in the CF compared to the healthy subjects. ΔAmil was greater with both albuterol and exercise when compared to baseline within both CF and healthy groups, but there was no significant difference in the ΔTCC response with either treatment. CONCLUSION: Both exercise and albuterol can alter ion regulation increasing Cl(-) secretion to a significant and similar degree in individuals with CF.

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Introducción: el score de sensibilidad genotípica (GSS) es una herramienta para predecir el resultado virológico del TARV. El objetivo de este estudio es comparar el GSS de tres tratamientos an-tirretrovirales (TARVs) en una población de embarazadas infectadas por VIH (EIV) naïve en Buenos Aires, Argentina. Materiales y Métodos: se analizaron las pruebas de resistencia de 47 EIV naïve en la ciudad de Buenos Aires (período 2008-2011), utilizan-do el algoritmo de la Universidad de Stanford-HIVdb program (pre-valencia de resistencia primaria del 21,2 %). La eficacia predicha de cada fármaco se computó como 1,00-0,75-0,50-0,25 y 0,00 para las cinco categorías HIVdb: desde susceptible a resistencia de alto nivel. El GSS se obtuvo con la suma de las puntuaciones de los fármacos individuales incluidos (GSS = 3, significa tres medicamentos total-mente activos). Tres TARVs se compararon: zidovudina+lamivudina más nevirapina (ART1), nelfinavir (ART2) o lopinavir/ritonavir (ART3). Resultados: se obtuvo un GSS de 3 en el 80,9 % con ART1 y el 91,5 % con ART2 y ART3. No hubo diferencia estadísticamente significati-va en la posibilidad de lograr un GSS de 3 entre los TARVs evaluados. Conclusiones: no hubo diferencia estadística en la probabilidad de proporcionar un régimen comple-tamente activo con un inhibidor de la proteasa o nevirapina. En nuestra opinión, un TARV con una alta barrera genética sería preferible en el contex-to de la alta prevalencia de resistencia primaria ob-servada

Background: The genotypic sensitivity score (GSS) is a tool to predict virological treatment outcome. The objective of this study is to compare the GSS of three antiretroviral treatment (ART) strategies in a population of naive pregnant women (NPW) in Buenos Aires city, Argentina. Methods: Resistance tests from 47 NPW were analyzed in the context of a sentinel resistance surveillance study in Buenos Aires city (period 2008-2011), considering the genotype interpretation system of the Stanford HIVdb program (prevalence of primary drug resistance of 21.2%). The predicted efficacy of each drug was scored either as 1.00-0.75-0.50-0.25 and 0.00 for the five HIVdb categories: from susceptible to high-level resistance. GSS was obtained with the sum of the scores for the individual drugs included in a regimen (GSS of 3 means three fully active drugs). GSS of three ARTs were compared: zidovudine+lamivudine plus either nevirapine (ART1), nelfinavir (ART2) or lopinavir/ritonavir (ART3). Results: A GSS of 3 was achieved in 80.9% with ART1 and 91.5% with both ART2 and ART3. There was no statistical difference in the possibility of achieving a GSS of 3 between the three ARTs evaluated. Conclusions: There was no statistical difference in the probability of providing a fully active regimen with either a protease inhibitor or nevirapine. In our opinion, an ART with a high genetic barrier backbone may be preferred in the context of the high prevalence of primary resistance observed

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BACKGROUND: Although exercise is a vital component of the therapy prescribed to individuals with cystic fibrosis (CF), it is not a priority due to a finite amount of treatment time and the view that exercise is not as beneficial as pharmacological treatments by many individuals with CF. We sought to compare the therapeutic benefits of exercise and their prescribed bronchodilator albuterol. METHODS: CF (n = 14) and healthy (n = 16) subjects completed three visits, a baseline screening with VO2 max test and two treatment visits. On the two treatment visits, subjects completed spirometry and diffusing capacity of the lungs for nitric oxide (DLNO) maneuvers either at baseline, 60, and 110 min post-albuterol administration, or at baseline and the midway point of three separate 15 min exercise bouts at low, moderate and vigorous intensity (25, 50 and 65% of the maximum workload, respectively). RESULTS: With moderate exercise the increase in DLNO was double (39 ± 8 vs 15  ± 6% change) and the level of bronchodilation similar (23% change) when compared to 110 min post-albuterol in individuals with CF. During exercise FVC became reduced (-309 ± 66 mL with moderate exercise) and the increase in FEV1 was attenuated (103 ± 39 vs 236 ± 58 mL, exercise vs. albuterol) when compared with the response to albuterol in individuals with CF. Epinephrine (EPI) release increased 39, 72 and 144% change with low, moderate and vigorous intensity exercise respectively for individuals with CF, but this increase was blunted when compared to healthy subjects. CONCLUSION: Our results suggest that moderate intensity exercise is the optimal intensity for individuals with CF, as low intensity exercise increases EPI less than 50% and vigorous intensity exercise is over taxing, such that airflow can be restricted. Although the duration of the beneficial effect is uncertain, exercise can promote greater improvements in gas diffusion and comparable bronchodilation when compared to albuterol.

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INTRODUCTION: Epithelial Na channels (ENaCs) play a crucial role in ion and fluid regulation in the lung. In cystic fibrosis (CF), Na hyperabsorption results from ENaC overactivity, leading to airway dehydration. Previous work has demonstrated functional genetic variation of SCNN1A (the gene encoding the ENaC α-subunit), manifesting as an alanine (A) to threonine (T) substitution at amino acid 663, with the αT663 variant resulting in a more active channel. METHODS: We assessed the influence of genetic variation of SCNN1A on the diffusing capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO), together with alveolar-capillary membrane conductance (DM), pulmonary capillary blood volume, and alveolar volume (VA) at rest and during peak exercise in 18 patients with CF (10 homozygous for αA663 (AA group) and 8 with at least one T663 allele (AT/TT group)). Because of the more active channel, we hypothesized that the AT/TT group would show a greater increase in DLCO, DLNO, and DM with exercise because of exercise-mediated ENaC inhibition and subsequent attenuation of Na hyperabsorption. RESULTS: The AT/TT group had significantly lower pulmonary function, weight, and body mass index than the AA group. Both groups had similar peak workloads, relative peak oxygen consumptions, and cardiopulmonary responses to exercise. The AT/TT group demonstrated a greater increase in DLNO, DLNO/VA, and DM in response to exercise (% increases: DLNO = 18 ± 11 vs 41 ± 38; DLNO/VA = 14 ± 21 vs 40 ± 37; DM = 15 ± 11 vs 41 ± 38, AA vs AT/TT, respectively). There were no differences between groups in absolute diffusing capacity measures at peak exercise. CONCLUSION: These results suggest that genetic variation of the α-subunit of ENaC differentially affects the diffusing capacity response to exercise in patients with CF.

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