Joseph Reisman

Prediction of Mortality in Patients with Cystic Fibrosis

BACKGROUND The majority of patients with cystic fibrosis die in early adulthood of lung disease. Lung transplantation is a treatment option for patients with advanced pulmonary disease, although the waiting period for organs may be as long as two years. Our purpose was to determine whether the risk of death due to respiratory failure could be predicted one or two years in advance on the basis of pulmonary function, blood gas levels, and nutritional status. METHODS The study cohort consisted of 673 patients followed between 1977 and 1989. In each patient, pulmonary function, blood gas levels, nutritional status, and vital status were assessed between 1977 and 1987. Cox proportional-hazards regression analysis was used to compute the relative risk of death within one or two years after particular measurements. The effects of age and sex on mortality were also included in the analysis. RESULTS One hundred ninety patients (28 percent) died during the study period. Overall, patients with a forced expiratory volume in one second (FEV1) less than 30 percent of the predicted value, a partial pressure of arterial oxygen below 55 mm Hg, or a partial pressure of arterial carbon dioxide above 50 mm Hg had two-year mortality rates above 50 percent. Among the laboratory measurements, the FEV1 was the most significant predictor of mortality, but age and sex were also significant in predicting risk. After adjustment for age and sex, the relative risk of death within two years was 2.0 (95 percent confidence interval, 1.9 to 2.2) for each decrement in the FEV1 of 10 percent below the predicted value. Among patients with the same FEV1, the relative risk of death was 2.0 (95 percent confidence interval, 1.5 to 2.6) in patients 10 years younger than other patients, and 2.2 (1.6 to 3.1) in female patients as compared with male patients. CONCLUSIONS Patients with cystic fibrosis should be considered candidates for lung transplantation when the FEV1 falls below 30 percent of the predicted value. Female patients and younger patients may need to be considered for transplantation at an earlier stage.

A Comparison of Inhaled Fluticasone and Oral Prednisone for Children with Severe Acute Asthma

BACKGROUND Inhaled corticosteroids are effective in the treatment of children with asthma. It is uncertain how inhaled corticosteroids compare with oral corticosteroids in the management of severe acute disease. METHODS We performed a double-blind, randomized trial involving 100 children five years of age or older who had severe acute asthma (indicated by a forced expiratory volume in one second [FEV1] that was less than 60 percent of the predicted value) and in whom the results could be evaluated. All were treated with an aggressive bronchodilator regimen and received one dose of either 2 mg of inhaled fluticasone through a metered-dose inhaler with a spacer or 2 mg of oral prednisone per kilogram of body weight. They were assessed hourly for up to four hours. RESULTS The mean (+/-SD) base-line FEV1 as a percentage of the predicted value was 46.3+/-12.5 in the fluticasone group (51 subjects) and 43.9+/-9.9 in the prednisone group (49 subjects). The FEV1 increased by a mean of 9.4+/-12.5 percentage points in the fluticasone group and by 18.9+/-9.8 percentage points in the prednisone group four hours after therapy (P< 0.001). None of the children in the prednisone group had a reduction in FEV1 as a percentage of the predicted value from base line to four hours, as compared with 25 percent of those in the fluticasone group (P<0.001). Sixteen (31 percent) of the children treated with fluticasone were hospitalized, as compared with five (10 percent) of those treated with prednisone (P=0.01). CONCLUSIONS Children with severe acute asthma should be treated with oral prednisone and not with inhaled fluticasone or a similar inhaled corticosteroid.

Efficacy of albuterol administered by nebulizer versus spacer device in children with acute asthma

The aim of this study was to compare the response to inhaled albuterol after administration by nebulizer with the response after administration by a metered-dose inhaler and spacer device (MDI-spacer) to children with acute asthma. In a double-blind fashion, 33 children (6 to 14 years of age) with forced expiratory volume in 1 second (FEV1) between 20% and 70% of predicted values, and who were seen in the emergency department with acute asthma, were studied. They were treated with aerosolized albuterol or placebo by MDI-spacer, followed immediately by albuterol or placebo administered by nebulizer with oxygen. The dose ratio for albuterol by MDI-spacer versus nebulizer was 1:5. Outcome measures included a clinical score, respiratory rate, arterial oxygen saturation, and FEV1, measured before and 10, 20, and 40 minutes after treatment. With the exception of heart rate (which increased in the nebulizer group and decreased in the MDI-spacer group (p < 0.05), no difference in the rate of improvement of clinical score, respiratory rate, arterial oxygen saturation, or FEV1 was noted during the 40-minute study period between children who received albuterol by nebulizer and those who received it by MDI-spacer. We conclude that spacers and nebulizers are equally effective means of delivering beta 2-agonists to children with acute asthma.

Nebulized albuterol in acute bronchiolitis

In a double-blind, placebo-controlled trial, 40 infants between 6 weeks and 24 months of age who had a first episode of wheezing and other signs and symptoms of bronchiolitis were randomly assigned to receive either nebulized albuterol (0.15 mg/kg/dose) or placebo (saline solution) for two administrations 1 hour apart. The albuterol therapy resulted in a significantly greater improvement in the accessory muscle score (decreases 0.70 vs decreases 0.30; p = 0.03), oxygen saturation (increases 0.71% vs decreases 0.47%; p = 0.01) after one dose, and in the accessory muscle score (decreases 0.86 vs decreases 0.37; p = 0.02), respiratory rate (decreases 19.6% vs decreases 8.0%; p = 0.016), and oxygen saturation (increases 0.76% vs decreases 0.79%; p = 0.015) after two doses of the drug. The response to therapy was similar in infants younger and those older than 6 months of age. The heart rate rose slightly more in the albuterol group (increases 7.76 from baseline) versus the placebo group (decreases 6.79). There were no other side effects of the treatment. Of the 34 children from whom nasal specimens were obtained by swab for viral identification, 24 had positive test results (21 for respiratory syncytial virus, 1 for parainfluenza, 1 for paramyxovirus, and 1 for influenza A). We conclude that nebulized albuterol constitutes a safe and effective treatment of infants with bronchiolitis.

Allergy in asthma: I. The dose relationship of allergy to severity of childhood asthma

The relationship between allergy and childhood asthma was investigated. We hypothesized that if allergy were a factor in aggravating asthma, we should find that allergy (defined by symptoms and numbers of positive prick skin tests) increased with increasing severity of asthma. One hundred forty-two children with asthma, referred to a pulmonologist and an allergist, 123 of whom were skin tested, were graded according to clinical severity and compared to a group of 29 normal individuals, 48 patients with allergic rhinitis, and 52 patients with cystic fibrosis. The 29 symptom-free individuals had only one positive skin test among them, whereas 65% of the clinic patients with asthma had three or more positive skin tests (p less than 0.001). This compared with 35.4% of the patients with rhinitis (p less than 0.001) and 14% of the patients with cystic fibrosis (p less than 0.001). There was an increase in the number and size of positive skin tests with increasing severity of asthma. Similarly, there was increased reporting of allergic symptoms, such as sensitivity to animals with increasing severity of asthma. These data indicate that atopy is associated with asthma in a crude dose-response fashion, and children with chronic, steroid-dependent asthma are often highly atopic, easily sensitized, and form IgE antibodies to a broad range of allergens.

Prevalence of abnormalities found by sinus x-rays in childhood asthma: lack of relation to severity of asthma

We examined the prevalence of abnormalities found by sinus x-rays in patients with asthma. The overall prevalence of abnormalities found was greater in the patients with asthma, 43 of 138 (31.2%), compared to control patients with dental problems, 0 of 50 (p less than 0.001). However, the percent of patients with abnormalities found by sinus x-rays was the same whether the asthma was mild, requiring minimal medication, or severe, requiring multiple medications. The results provide no support for the hypothesis that sinusitis, as detected by abnormalities found by sinus x-rays, aggravates asthma and promotes increased need for medication to control the asthma.

Sequential pulmonary function measurements during treatment of infantile chronic interstitial pneumonitis

Three infants with histologically confirmed chronic interstitial pneumonitis were treated with monthly intravenously administered high doses of methylprednisolone with or without daily hydroxychloroquine therapy. We applied the multiple occlusion technique to measure the static respiratory system compliance, and the end-inspiratory occlusion technique to measure passive respiratory system compliance, resistance, and time constant. When assessed by clinical criteria and pulmonary function measurements, all three patients showed improvement with this treatment. Clinical improvement was associated with an increase in respiratory system compliance as measured by both techniques (60% to 100% increase in all patients). The passive respiratory resistance and the time constant did not closely reflect the clinical course. We conclude (1) that high doses (pulses) of methylprednisolone and daily oral doses of hydroxychloroquine are effective in the treatment of infantile chronic interstitial pneumonitis and (2) that the respiratory system compliance, measured by both pulmonary function techniques, correlates well with the response to treatment and change in clinical status.

Hypoalbuminemia at initial examination in patients with cystic fibrosis.

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Hepatic abscess and cystic fibrosis.

Extrapulmonary infection is rare in cystic fibrosis. We describe two adult patients with cystic fibrosis whose course was complicated by the development of liver abscesses. The possible aetiology of these abscesses is discussed and the diagnosis, treatment and prognosis of pyogenic hepatic abscess is briefly reviewed.

Omalizumab treatment of moderate to severe asthma in the adolescent and pediatric population

Background In Canada and the US, omalizumab is indicated for adults and adolescents (>12 years of age) with moderate to severe persistent allergic asthma. In the EU, omalizumab has been approved for children (age 6 – 11 years) since 2009. The pediatric population within Canada and the United States has very few treatment options available for severe asthma. Current treatments options can lead to other health concerns such as adrenal insufficiency and osteoporosis. These cases demonstrate that early treatment of moderate to severe asthma with omalizumab is an effective treatment and can help to prevent or reverse damage done by long-term use of other treatment options.