Survival of individuals receiving long-term mechanical ventilation

The reports published to date support the concept that LTMV can extend life for patients with respiratory insufficiency, particularly adults and children with neuromuscular and chest wall diseases. The impact of LTMV on survival in patients with obstructive lung diseases, such as COPD and bronchiectasis, is less clear and deserves further study. For all disease states, research is needed to determine the characteristics of patients who are most likely to benefit from LTMV and whether one method of ventilation is superior to another. In addition to survival, other important outcomes, such as patient satisfaction, quality of life, and costs associated with LTMV, should be assessed in future long-term studies.     

Quality of life measured with a generic instrument (Short Form-36) improves following pulmonary rehabilitation in patients with COPD

STUDY OBJECTIVES: The purpose of this study was to evaluate the effects of a 3-week comprehensive pulmonary rehabilitation program on quality of life as measured by the Short Form-36 (SF-36) in patients with COPD. DESIGN AND SETTING: We report on the outcomes of 37 consecutive patients referred for pulmonary rehabilitation at a respiratory specialty medical center. PATIENTS: Thirty-seven patients (mean age, 66 years) with COPD and severe airflow limitation (mean +/- SE FEV(1), 29.6 +/- 1.8% of predicted) were studied. INTERVENTIONS: Rehabilitation consisted of a 3-week pulmonary rehabilitation program incorporating 12 exercise sessions, each of which included bicycle ergometer exercise training, upper-extremity training, strength training, and stretching, along with psychosocial counseling and education. MEASUREMENTS AND RESULTS: The Health Status Index (SF-36) and 6-min walk test were completed before and after rehabilitation. There was an improvement in five of the nine quality-of-life subscales of the SF-36 following pulmonary rehabilitation. Although there was an improvement in functional capacity as measured by the 6-min walk, there was no correlation between improvement in quality of life and improvement in functional capacity. There was no correlation between FEV(1) and improvement in walk distance, but there was a correlation between FEV(1) and improvement in SF-36 physical function and energy/fatigue subscales. CONCLUSION: Health-related quality of life assessed by the SF-36, a general measure of quality of life, improves following an intensive 3-week pulmonary rehabilitation program. Use of the SF-36 allows comparison of the results of pulmonary rehabilitation to therapeutic interventions in patients with other medical disorders.     

The efficacy and safety of inhaled fluticasone propionate/salmeterol and ipratropium/albuterol for the treatment of chronic obstructive pulmonary disease: an eight-week, multicenter, randomized, double-blind, double-dummy, parallel-group study

BACKGROUND: The pathology of chronic obstructive pulmonary disease (COPD) includes both obstructive and inflammatory components. OBJECTIVE: The aim of this study was to confirm the findings of a previous study that compared the efficacy of a combination of 2 short-acting bronchodilators with the use of an inhaled corticosteroid and a long-acting beta-agonist in the treatment of COPD. METHODS: We conducted an 8-week, multicenter, randomized, double-blind, double-dummy, parallel-group study of subjects with moderate to severe COPD to compare fluticasone propionate/salmeterol 250/50 microg BID (FSC) with ipratropium/albuterol 36/206 microg QID (IB/ALB). The primary efficacy measure was morning preadministration forced expiratory volume in 1 second (FEV(1)). Secondary measures were morning peak expiratory flow (PEF), 6-hour FEV(1) AUC, percentage of symptom-free nights, Transition Dyspnea Index (TDI) score, and overall daytime symptom score. Additional measures included sleep symptoms, supplemental albuterol use, and nighttime awakenings due to respiratory symptoms. Safety evaluations were based on clinical adverse events and COPD exacerbations. RESULTS: Baseline characteristics were similar between the FSC (n = 180) and IB/ALB (n = 181) groups, including mean age (63.7 and 65.4 years, respectively), mean body weight (81 and 79 kg, respectively), screening pulmonary function (mean [SD], 43.7% [14.2%] and 41.6% [13.4%] of predicted FEV(1)), race (82% and 91% white), and sex (64% and 62% male). FSC resulted in greater improvements in morning preadministration FEV(1), morning PEF, and 6-hour FEV(1) AUC (all, P < 0.001), TDI score (P = 0.026), overall daytime symptom score (P = 0.024), percentage of symptom-free nights (P = 0.010), nighttime awakenings due to respiratory symptoms (P = 0.002), sleep symptom score (P = 0.003), and percentage of days and nights without rescue albuterol use compared with IB/ALB (P = 0.021 and P < 0.001, respectively). Compared with day 1, the FEV(1) AUC at week 8 increased by 0.38 L-h with FSC and decreased by 0.18 L-h with IB/ALB (P < 0.001 between groups). The type and incidence of adverse events were similar between the 2 groups. One or more adverse event was reported for 81 (45%) and 85 (47%) subjects in the FSC and IB/ALB groups, respectively. CONCLUSION: In this 8-week study, subjects with moderate to severe COPD experienced greater improvements in lung function and symptom measures with FSC than with IB/ALB.     

Inhaled corticosteroids in chronic obstructive pulmonary disease

The effectiveness of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD) remains controversial. Randomized controlled trials, meta-analyses, medication withdrawal studies, and observational reports have examined this question, with mixed results. Observational studies have been subject to criticism because of study design involving immortal time bias. Some randomized controlled trials suggest small benefits in lung function and health status, and a reduction in the rate of acute exacerbations of COPD and mortality, but their incomplete follow-up and statistical methods have been criticized. The greatest benefits of ICS in COPD have been reported with use of ICS and long-acting beta-agonist combination therapy, although no benefit was found for the primary outcome studied under the most rigorous methodology by the recent TORCH and Optimal randomized trials. Thus, although future randomized trials will need to be conducted with the most rigorous methodology for all outcomes, much uncertainty remains regarding the potential benefits of ICS in COPD.     

Different mRNA expression profiling of nuclear retinoid,thyroid, estrogen and PPARgamma receptors,their coregulators and selected genes in rat liver and spleen in response to short-term in vivo administration of 13-cis retinoic acid

Retinoic acids (RAs) and also their analogs (synthetic retinoids and rexinoids) have been regarded as major therapeutic and/or chemopreventive agents and can regulate a number of diverse processes—such as immune system, hormonal systems. In this work we describe different effects of short-term treatment of Wistar male rats with 13-cis retinoic acid on the regulation of retinoic acid receptors (RARs), retinoid-X receptors (RXRs), thyroid hormone receptors (TRs), ERs, 5′-DI, EGFR and erb-B2/neu genes in liver and/or spleen. Using RT-PCR analysis we have found that administration of 13-cis retinoic acid enhanced expression of RARβ and PPARγ mRNA, and decreased expression of RARα, RARγ, RXRβ and TRβ mRNA in liver. On the other hand, in spleen this treatment resulted in decreased expression of RARα, RARβ, RARγ, TRα and ERβ mRNA. Our findings indicate distinct modulation of various signal pathways by short-term administration of 13cRA, which also differ in spleen when compared to liver. We suggest that even a short-term treatment of rats with 13cRA may affect a reasonable number of steps in retinoid signaling pathways, a number of which might be very likely extended by long-term treatment of mammals by 13-cis retinoic acid.     

Mechanical ventilation in the home

Despite advances in the application of mechanical ventilation as a short-term, life-saving technique, intensive care units are increasingly faced with patients who cannot be weaned from ventilatory assistance and who require mechanical ventilation as a long-term, life-supporting necessity. Because of limited resources in health care facilities for the management of chronic ventilator-assisted individuals, home care has become an important option. With careful selection of appropriate candidates, home care for ventilator-assisted individuals can result in not only decreased respiratory symptoms, reduction in hospitalization, and improved physiologic measures, but also an improved quality of life with substantial survival and a reduction in the costs of medical care.     

Respiratory consequences of abdominal hernia in a patient with severe chronic obstructive pulmonary disease

The diaphragm is the most important muscle of respiration. It is believed that the abdominal contents affect diaphragmatic contraction by helping determine its length tension state and by acting as a fulcrum for this muscle to lift the rib cage and thereby increase lung volume. In support of these concepts we describe a patient with severe chronic obstructive pulmonary disease and a large midline hernia of the abdomen who, when standing, had a gastric pressure (Pg) of 4 cm H2O and a maximal transdiaphragmatic pressure (Pdimax) of 14 cm H2O. This was associated with an O2 saturation of 82%, lower thoracic and upper abdominal paradoxical breathing, and severe dyspnea. Once the hernia was reduced there was a rise in Pg to 12 cm H2O, of Pdimax to 27 cm H2O, and of O2 saturation to 89%. There was normalization of the breathing pattern and a decrease in dyspnea. Reduction of this patient's abdominal hernia resulted in an increase in her exercise tolerance.     

Contaminated medication nebulizers in mechanical ventilator circuits. Source of bacterial aerosols

The contamination rates of medication nebulizers inserted into mechanical ventilator circuits were studied. Semiquantitative techniques were used to sample the reservoir fluid from in-line nebulizers during the first 24 hours after a circuit change. In the initial survey, high levels of contamination (organism concentrations above 10(3)/ml) were present in 13 (68 percent) of the 19 nebulizer reservoirs, and bacterial aerosols were produced by 10 (71 percent) of 14 nebulizers. Gram-negative bacilli were the predominant organisms isolated. Nebulizer contamination originated primarily from reflux of contaminated condensate in the ventilator circuit. When nebulizers were cleaned after each treatment, a reduced rate of contamination was found. Small bacterial aerosols (less than 3 microns in size) were produced in vitro after inoculation of nebulizers with gram-negative bacilli in concentrations isolated from in-use nebulizers. Contaminated in-line medication nebulizers generate small-particle bacterial aerosols that may increase the risk of ventilator-associated pneumonia and therefore should be cleaned or disinfected after each treatment rather than every 24 hours.