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Biomedical subjects

Donald W Cockcroft

Publications and source records attributed to Donald W Cockcroft.

13 recordsLinked to original sources
PubMed2004

Differences in respiratory symptoms and pulmonary function in children in 2 Saskatchewan communities.

BACKGROUND: Asthma prevalence is known to vary among different geographical regions both nationally and internationally. However, there is limited understanding of the nature of differences within geographical regions. OBJECTIVE: To evaluate the prevalence of asthma in 2 prairie communities and differences in the patterns of respiratory symptoms between the communities. METHODS: A cross-sectional questionnaire survey was sent through schools in Estevan and Swift Current, Saskatchewan, to parents of 2,231 children in grades 1 to 6. Asthma prevalence was determined by questionnaire report of physician-diagnosed asthma. Pulmonary function tests (PFTs) using spirometry were conducted in children in grades 1 to 4. To evaluate respiratory morbidity without the use of a diagnostic label, similar comparisons were made between communities for respiratory symptoms. RESULTS: The overall response rate to the survey questionnaire was 91.3%. The prevalence of ever asthma in Estevan was 21.4% (95% confidence interval [CI], 20.1%-22.7%) compared with 16.2% (95% CI, 15.1%-17.3%) in Swift Current. A higher proportion of girls in Estevan (19.7%; 95% CI, 17.9%-21.5%) compared with girls in Swift Current (12.5%; 95% CI, 11.1%-13.9%) reported a history of asthma. There was no difference found between towns for boys. These findings were supported by findings for respiratory symptoms, including wheeze and cough. For both boys and girls, the forced expiratory flow at 25% to 75% of forced vital capacity and the ratio of forced expiratory volume in 1 second to forced vital capacity were lower in Estevan compared with Swift Current. CONCLUSIONS: Differences in the distribution of childhood asthma can be found within regions. These results are strengthened by PFTs and cannot be fully explained by diagnostic biases.

Asthma↗
PubMed2004

Nonspecific interstitial pneumonia and usual interstitial pneumonia with mutation in surfactant protein C in familial pulmonary fibrosis.

Nonspecific interstitial pneumonia, a recently described form of idiopathic interstitial pneumonia, is characterized by uniform involvement of the alveolar septae with interstitial inflammation and variable amounts of fibrosis. Histological observations differentiate nonspecific interstitial pneumonia from usual interstitial pneumonia and clinically, patients with a nonspecific interstitial pneumonia pattern show better prognosis than those with usual interstitial pneumonia. We have genetically analyzed a family with a history of usual interstitial pneumonia. Most of the patients presented as adults and their biopsies showed a pattern consistent with usual interstitial pneumonia. However, three family members presented in early childhood and their biopsies revealed a nonspecific interstitial pneumonia pattern. The inheritance pattern of usual interstitial pneumonia is consistent with autosomal dominant inheritance with variable expression. DNA sequence analyses of the surfactant protein C gene in children with nonspecific interstitial pneumonia and adults with usual interstitial pneumonia exhibit a common heterozygous mutation located in exon 5. The mutation causes a Leu188 to Gln188 change in the carboxy-terminal region of prosurfactant protein C, possibly affecting peptide processing. These observations suggest that individuals with this particular mutation in surfactant protein C gene might be at increased risk of interstitial lung disease of variety of types.

Adolescent↗
PubMed2003

Sex differences in asthma, atopy, and airway hyperresponsiveness in a university population.

BACKGROUND: A male predominance in atopy, a preadolescent male predominance in asthma, and a female predominance in airway hyperresponsiveness (AHR) have been previously documented, mostly in separate populations. OBJECTIVE: We examined gender differences in a single population of 500 randomly selected university students from a previous publication which addressed sensitivity and specificity of histamine bronchoprovocation (Cockcroft et al. J Allergy Clin Immunol. 1992;89:23-30). METHODS: In these 500 subjects (age 21.8 +/- 1.5 years) we assessed gender differences in asthma, atopy, and AHR. We compared our findings with those in the literature from a PUBMED search using the keywords gender, asthma, atopy, AHR, and bronchial reactivity. RESULTS: A diagnosis of asthma made by another physician was seen in 31, a male-to-female ratio of 2.9:1 (P = 0.004). Our definition of asthma increased the total to 52 and reduced the male-to-female ratio to 1.2:1. Atopy was seen in 190, male-to-female ratio of 1.5:1 (P = 0.001). Borderline to mild AHR had a female predominance with a male-to-female ratio of 1:1.5 (P = 0.02), whereas moderate AHR had a marked predominance with a male-to-female ratio of 7:1 (P = 0.03). CONCLUSIONS: In our population, the associations among gender and asthma, atopy, and AHR were similar to those seen in the literature with the exception of males having more severe AHR. This may be the one factor contributing to the higher prevalence of asthma (including previous doctor-diagnosed asthma in our population) in boys and young men.

Adult↗
PubMed2003

A case report of wegener granulomatosis treated only with corticosteroids for 30 years.

BACKGROUND: Wegener granulomatosis is a systemic vasculitis classically described as involving the upper and lower respiratory tracts together with glomerulonephritis. Its poor prognosis was marginally improved with the use of corticosteroids, and long-term remission was not achieved until the introduction of cytotoxic agents. Generalized or systemic Wegener granulomatosis has a worse prognosis than those limited to the respiratory tracts. OBJECTIVE: To report the case of an individual who we suspect has a 30-year history of Wegener granulomatosis treated only with prednisone. METHODS: A literature search was performed with PubMed using the keywords Wegener granulomatosis, survival, prognosis, and treatment. RESULTS: Our patient is alive 32 years after her initial symptoms of vasculitis. She has been taking daily prednisone only for the majority of this time. Our clinical diagnosis of Wegener granulomatosis is based on the history and very high antineutrophil cytoplasmic antibody with the cytoplasmic pattern. CONCLUSIONS: There may be variants of generalized Wegener granulomatosis that survive with less aggressive treatment.

Aged↗
PubMed2003

The effects of an anti-CD11a mAb, efalizumab, on allergen-induced airway responses and airway inflammation in subjects with atopic asthma.

BACKGROUND: Efalizumab is a humanized IgG(1) mAb against the lymphocyte function antigen-1 (LFA-1) alpha chain, CD11a. Blocking of LFA-1/intercellular adhesion molecule interactions could inhibit asthmatic inflammation by blocking adhesion and activation of LFA-1-positive leukocytes. OBJECTIVE: A randomized, double-blinded, placebo-controlled, parallel group, multicenter study investigated the effects of efalizumab on allergen-induced airway responsiveness and airway inflammation. METHODS: Thirty-five nonsmoking subjects with mild allergic asthma were randomized to receive efalizumab (n = 24) or placebo (n = 11) in 8 weekly subcutaneous doses (0.7 mg/kg conditioning dose followed by 7 weekly doses of 2.0 mg/kg). Allergen challenges were performed at screening and after 4 and 8 weeks of treatment. Samples of sputum (n = 18 subjects) and blood (n = 35 subjects) were collected the day before challenges, and sputum was collected again at 7 and 24 hours after each challenge. Nonparametric tests were used to compare allergen-induced differences between efalizumab and placebo groups. RESULTS: Subjects receiving efalizumab developed headache (48%) and flu syndrome (28%) compared to subjects receiving placebo (0%). After 8 weeks of efalizumab, the maximum late percent fall in FEV(1) (late asthmatic response) was inhibited by 50%, but neither the late response nor the late area under the curve was statistically different than placebo (P =.098 and.062, respectively). Efalizumab had no effect on the maximum early percent fall in FEV(1) (early asthmatic response) or early area under the curve compared to placebo (P >.59). Efalizu-mab significantly reduced the postallergen increase in sputum EG2-positive cells and metachromatic cells (P <.05). No other comparisons were statistically different. CONCLUSIONS: Blocking of LFA-1/intercellular adhesion module interactions by efalizumab inhibits the development of allergen-induced cellular inflammatory responses measured in induced sputum and might attenuate the late asthmatic response. Larger studies are needed to confirm this.

Adult↗
PubMed2003

Development of a methacholine challenge method to minimize methacholine waste.

BACKGROUND: The standard 2-min tidal breathing methacholine challenge utilizes 3 mL to produce an output of 0.26 mL per 2 min, resulting in a substantial amount of methacholine being discarded. OBJECTIVE: To develop a method with reduced methacholine waste and to compare it to the standard method. METHODS: Twelve subjects with mild, well-controlled asthma volunteered for this investigation. They underwent three methacholine challenges in random order. The first challenge was the conventional 2-min tidal breathing method using 3 mL of doubling concentrations inhaled for 2 min at 5-min intervals. The first modification utilized 1.5 mL of quadrupling concentrations inhaled for 1 min and then 2 min, keeping the time interval constant at 3 min between completion of one inhalation and commencement of the next inhalation. The second modification utilized 1.5 mL of eightfold concentration step-ups inhaled for 30 s, 60 s, and 120 s with a time interval of 3 min between completion of one inhalation and commencement of the next inhalation. For each method, the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)) was calculated based on a 2-min equivalent-dose inhalation. RESULTS: There was no significant difference in the geometric mean PC(20) (1.5 mg/mL, 1.6 mg/mL, and 1.6 mg/mL for the three methods, respectively; p = 0.47). The quadrupling concentration method was preferred because it was less subject to error than the other modification. CONCLUSION: The amount of methacholine discarded during a methacholine challenge can be reduced by two thirds by decreasing the volume from 3 to 1.5 mL, and by using quadrupling concentrations inhaled either with quadrupling-dose step-ups, or with doubling-dose step-ups by using sequential 1-min and 2-min inhalations.

Adult↗
PubMed2003

Bronchoprovocation methods: direct challenges.

Inhalation challenges with direct-acting stimuli histamine and methacholine are widely used to measure airway responsiveness. Three widely used methods (2-min tidal breathing method, breath-activated dosimeter method, hand-held manual nebulizer) are described. Careful standardization is important so as to best differentiate normal from increased airway responsiveness and to permit comparison between methods. With current methods standardized as suggested by the ATS, a methacholine (or histamine) PC(20) > 16 mg/mL is considered normal. A PC(20) < 16 mg/mL is highly sensitive for current symptoms of asthma. Interpretation of methacholine or histamine inhalation test requires that symptoms be current (within a few days) and that FEV(1) be normal.

Administration, Inhalation↗
PubMedDate not supplied

Microscopic pulmonary tumour embolism: an unusual presentation of thymic carcinoma.

The present report describes the first reported case of microscopic pulmonary tumour embolism (MPTE) from thymic carcinoma. The carcinoma was discovered during an autopsy in a 55-year-old man who had undergone surgery for a pilonidal sinus two weeks before presentation. Pulmonary thromboembolism was suspected. This case was unusual because MPTE has never before been associated with thymic carcinoma, MPTE was the first clinical indication of an occult malignancy, and the clinical presentation was that of sudden onset of dyspnea associated with acute cor pulmonale. The cause of death was determined to be hypoxia secondary to extrinsic compression of the right pulmonary artery and extensive tumour emboli in the small arteries, arterioles and venules of the pulmonary parenchyma. A review of the clinical presentation and diagnosis of MPTE is included.

Fatal Outcome↗
PubMedDate not supplied

Formoterol thrice weekly does not result in the development of tolerance to bronchoprotection.

BACKGROUND: Loss of bronchoprotection routinely follows regular treatment with beta2-agonists. There are no data on the effects on bronchoprotection for thrice weekly use of a beta2-agonist. METHODS: A double-blind, randomized, placebo controlled crossover trial was conducted to investigate the effects of thrice weekly administration of 12 microg of formoterol versus placebo on bronchoprotection against methacholine. As an expected positive control, formoterol 12 microg once daily was also evaluated. RESULTS: There was no significant difference versus placebo in the bronchoprotective effects of 12 microg of formoterol administered on day 8, following daily treatment for seven days or treatment every other day (analysis of variance P=0.34). However, a nonsignificant trend towards lower concentration of methacholine that caused a 20% fall in forced expiratory volume in 1 s developed only following the daily formoterol dosing. CONCLUSIONS: Thrice weekly dosing does not result in the development of tolerance to bronchoprotection against the direct acting stimulus methacholine.

Administration, Oral↗