Cara Cassino - Academia.edu (original) (raw)

Papers by Cara Cassino

COPD, 2004

An accelerated loss of lung function is one of the defining characteristics of chronic obstructiv... more An accelerated loss of lung function is one of the defining characteristics of chronic obstructive pulmonary disease (COPD). To date, the only successful intervention shown to conclusively attenuate the loss of lung function over time is smoking cessation. Pharmacological interventions including inhaled corticosteroids and ipratropium bromide have not altered the rate of decline of lung function. Tiotropium is an inhaled anticholinergic that provides 24-hour bronchodilation with once-daily dosing due to prolonged muscarinic M3 receptor blockade. Controlled clinical trials have suggested sustained efficacy for periods of up to one year. We therefore initiated a four-year, controlled clinical trial (UPLIFT, Understanding the Potential Long-Term Impacts on Function with Tiotropium) in patients with COPD to evaluate the long-term effects of tiotropium on the rate of decline in lung function and health status as well as the frequency of exacerbations. The design of such large, long-term ...

D61. ANIMAL MODELS OF PULMONARY ARTERIAL HYPERTENSION: NEW IDEAS AND INSIGHTS, 2010

Progression of pulmonary hypertension is associated with increased proliferation and migration of... more Progression of pulmonary hypertension is associated with increased proliferation and migration of pulmonary vascular smooth muscle cells. PDGF is a potent mitogen and involved in this process. We now report that the PDGF receptor antagonist STI571 (imatinib) reversed advanced pulmonary vascular disease in 2 animal models of pulmonary hypertension. In rats with monocrotaline-induced pulmonary hypertension, therapy with daily administration of STI571 was started 28 days after induction of the disease. A 2-week treatment resulted in 100% survival, compared with only 50% in sham-treated rats. The changes in RV pressure, measured continuously by telemetry, and right heart hypertrophy were reversed to near-normal levels. STI571 prevented phosphorylation of the PDGF receptor and suppressed activation of downstream signaling pathways. Similar results were obtained in chronically hypoxic mice, which were treated with STI571 after full establishment of pulmonary hypertension. Moreover, expression of the PDGF receptor was found to be significantly increased in lung tissue from pulmonary arterial hypertension patients compared with healthy donor lung tissue. We conclude that STI571 reverses vascular remodeling and cor pulmonale in severe experimental pulmonary hypertension regardless of the initiating stimulus. This regimen offers a unique novel approach for antiremodeling therapy in progressed pulmonary hypertension.

Pulmonary Pharmacology & Therapeutics, 2009

Background: The magnitude of tiotropium (1) induced bronchodilation and (2) protection against dy... more Background: The magnitude of tiotropium (1) induced bronchodilation and (2) protection against dynamic hyperinflation in COPD phenotypes has not been studied.

Pharmacotherapy, 2005

To examine electrocardiographic findings after short-and long-term tiotropium therapy in patients... more To examine electrocardiographic findings after short-and long-term tiotropium therapy in patients with chronic obstructive pulmonary disease (COPD), and to establish previously reported symptomatic efficacy. Design. Randomized, double-blind, placebo-controlled, parallel-group study. Setting. Twelve outpatient investigational centers in the United States. Patients. One hundred ninety-six patients with COPD. Intervention. Patients received either tiotropium 18 µg once/day or placebo, delivered by the HandiHaler device. Measurements and Main Results. Electrocardiography (predose and 5 min postdose) and 24-hour Holter monitoring were performed at baseline and after 8 and 12 weeks of treatment with tiotropium 18 µg once/day or placebo. Efficacy measures (spirometry, global COPD ratings, scores on the EuroQol Health Questionnaire [EQ-5D], albuterol inhaler as needed) were included to demonstrate that the study population exhibited the characteristic improvements observed in previous tiotropium studies. Mean baseline forced expiratory volume in 1 second (FEV 1 ) was 1.03 L. Mean changes in heart rate from baseline were similar in both groups. No differences were noted in the percentage of patients developing rhythm or conduction abnormalities detected with electrocardiography or Holter monitoring. Frequency of premature beats and mean maximal changes in PR, QRS, QT, QTcB, and QTcF intervals were similar in both groups. No patients developed new-onset QT or QTc intervals greater than 500 msec, and no differences were noted in the percentage of patients developing new QT prolongation less than 30 msec, 30-60 msec, or greater than 60 msec. At 12 weeks, predose and postdose improvements in FEV 1 were 184 and 265 ml, respectively, with tiotropium versus placebo (p<0.001). Physician and patient global COPD ratings and the EQ-5D visual analog scale scores were improved with tiotropium (p<0.05); as-needed albuterol was reduced by 25% relative to placebo (p<0.05). Conclusion. Tiotropium provided spirometric and symptomatic benefits in patients with COPD and was not associated with evidence of electrocardiographic changes in heart rate, rhythm, QT intervals, or conduction.

Journal of Asthma, 1997

We evaluated the effects of maternal asthma on specific parameters of family function including t... more We evaluated the effects of maternal asthma on specific parameters of family function including the children's school attendance and mother's performance of basic parenting tasks. A case-controlled study of mothers with asthma (MA; n = 24) with children under the age of 13 and matched mothers without asthma (CM; n = 27) was performed. Children of mothers with asthma had a significantly impaired ability to attend school compared to children of control mothers (odds ratio = 15, 95% CI). Twenty-two percent of MA reported that their asthma caused their children to miss school at least once per month. In addition, 27% of MA reported that their children were regularly late for school because of the mother's asthma. Only 5% of the control mothers reported that their health caused their children to miss school, and none reported lateness. Asthma also impaired the ability of the MA to perform basic parenting tasks such as dressing children and preparing meals for children. These adverse effects of parental asthma on children's school attendance and parenting represent previously unappreciated indirect costs of asthma and may have immediate as well as future consequences.

European Respiratory Journal, 2008

The degree of acute improvement in spirometric indices after bronchodilator inhalation varies amo... more The degree of acute improvement in spirometric indices after bronchodilator inhalation varies among chronic obstructive pulmonary disease (COPD) patients, and depends upon the type and dose of bronchodilator and the timing of administration.

American Journal of Respiratory and Critical Care Medicine, 2000

Airway and alveolar inflammation have been described in asthma. Prolonged inflammation may lead t... more Airway and alveolar inflammation have been described in asthma. Prolonged inflammation may lead to airway remodeling, which can result in physiologic abnormalities. Elderly lifetime nonsmokers are an ideal population in which to examine the consequences of longstanding asthma. To test the hypothesis that airflow limitation and hyperinflation are associated with the duration of asthma, we evaluated airflow and lung volumes in a cohort of elderly asthmatic individuals. All subjects were > 60 yr of age and were lifetime nonsmokers (n = 75). Patients with asthma of long duration (LDA; n = 38) had asthma for >/= 26 yr (median = 40.0 yr); patients with asthma of short duration (SDA; n = 37) had asthma for < 26 yr (median = 9 yr). Patients with LDA had a significantly lower FEV(1)% predicted than did those with SDA (59.5 +/- 2.6% versus 73.8 +/- 3.1% [mean +/- SEM], respectively; p < 0.007). Regression analysis demonstrated that duration of asthma was inversely associated with FEV(1)% predicted (r = 0.264, p < 0.03). After bronchodilator administration, the patients with LDA continued to show airflow obstruction (FEV(1)% predicted = 65.4 +/- 2.9). Only 18% of patients with LDA attained a normal postbronchodilator FEV(1), whereas 50% of those with SDA were able to do so (p < 0.003). The FRC% predicted was significantly higher in subjects with LDA than in those with SDA (142.9 +/- 5.6 versus 124.1 +/- 4.4, respectively, p < 0.01). Multiple regression analysis revealed an association between FRC and duration of asthma that was independent of the degree of airflow limitation. These data suggest that the duration of asthma is associated with the degree of airflow limitation and hyperinflation. Moreover, these abnormalities can become irreversible over time, and may reflect distal airway and/or parenchymal changes as well as proximal airway remodeling.

American Journal of Respiratory and Critical Care Medicine, 1999

The association between ambient ozone (O3) and hospital use for asthma in children and adults is ... more The association between ambient ozone (O3) and hospital use for asthma in children and adults is well documented. The question remains of whether there are susceptible subpopulations of asthmatic individuals who are particularly vulnerable to high O3 levels. Because tobacco use was prevalent in our cohort of inner-city adult asthmatic individuals (n = 1,216) in New York City (NYC), we investigated whether cigarette smoking was an effect modifier for asthma morbidity. We examined the relationship between personal tobacco use and O3-associated emergency department (ED) use for asthma in public hospitals in NYC. Three subpopulations were defined: never smokers (0 pack-yr), heavy smokers (>/= 13 pack-yr) and light smokers (< 13 pack-yr). Time-series regression analysis of ED use for asthma and daily O3 levels was done while controlling for temperature, seasonal/long-term trends, and day-of-week effects. Heavy smokers displayed an increased relative risk (RR) of ED visits for asthma in response to increases in 2-d lagged O3 levels (RR per 50 ppb O3 = 1.72; 95% confidence interval: 1.13 to 2.62). Logistic regression analysis confirmed that heavy cigarette use was a predictor of ED use for asthma following days with high O3 levels. Although adverse health effects of ambient O3 have also been documented in asthma populations not using cigarettes (e.g., children), our results suggest that in adult asthmatic individuals, heavy personal tobacco use may be an effect modifier for O3-associated morbidity.

Pulmonary Pharmacology and Therapeutics, 2008

Background: The potential of anticholinergics to provide bronchodilatory benefits over short-acti... more Background: The potential of anticholinergics to provide bronchodilatory benefits over short-acting b 2 -agonists (SABA) alone in patients with moderate-to-severe persistent asthma has not been well defined. Methods: An outpatient, randomized, double-blind, single-dose, crossover study in adult asthmatics with moderate-to-severe obstruction despite treatment with inhaled corticosteroids (ICS) was conducted comparing the fixed combination of ipratropium and albuterol (IB+ALB) to albuterol alone (ALB). Serial spirometry was performed over 6 h. SABA were withheld for 8 h, ICS and LABA for 24 h. Results: A total of 113 patients were randomized, 106 completed the study (males n ¼ 47; mean7SD age ¼ 51713 years). Mean7SD baseline FEV 1 ¼ 1.470.5 L (49712% predicted). IB+ALB resulted in significantly greater improvements over ALB in the average improvement over baseline in FEV 1 as approximated from the area under the curve from 0 to 6 h after drug administration (72 ml, po0.01) and mean peak FEV 1 response (55 ml, po0.01) as well as higher FEV 1 responses at individual time points from 0.5 to 6 h postdose (po0.01 for all). Time to onset of response was similar between groups but time to peak and duration of response were longer with IB+ALB versus ALB (120 versus 60 min and 245 versus 106 min, respectively). Conclusion: IB+ALB resulted in significantly greater improvement in FEV 1 and longer duration of response compared to ALB alone in patients with moderate-to-severe persistent asthma (Trial number: 1012.50; ClinicalTrial.gov NCT00096616).