Effect of dry powder inhaler resistance on the inspiratory flow rates and volumes of cystic fibrosis patients of six years and older.

Several inhaled drugs for use by cystic fibrosis (CF) patients are formulated for nebulizer use only. This therapy is time consuming and includes the risk of contamination of the nebulizers. Dry powder inhalers (DPI) can be an attractive alternative for CF drugs. Inhaled flow rate and volume, and the device resistance are important determinants for optimal dispersion of drug from a DPI. It is important to understand how these variables interact in the CF population in order to properly design a new DPI formulation targeted for these patients. The objective of this study was to assess the inspiratory variables of a representative population of CF subjects 6 years and older with varying degrees of lung disease while inhaling through resistances that simulate DPI devices. Ninety-six stable CF patients were enrolled, ages 6-54 years, FEV(1) 19-126% predicted. Subjects inhaled forcefully through four different resistances (0.019, 0.024, 0.038, and 0.048 kP(0.5)/LPM, respectively), while inspiratory time (IT(DPI)), peak inspiratory flow (PIF(DPI)), and volumes (V(DPI)) were measured. For any resistance, inspired V(DPI) increased with the older age groups; PIF(DPI) was similar between adults and adolescents but lower in the children. Subjects with lower FEV(1) had lower V(DPI) and PIF(DPI). As resistance increased, PIF(DPI) decreased, IT(DPI) increased, with no significant change in V(DPI). At the lowest resistance mean PIF(DPI) was 105 LPM (range 45-163) for all patients; 112 LPM (range 75-163) in adults; and 89 LPM (45-126) in children. Mean inspired V(DPI) was 1.75 L for all patients; 2.2 L (0.8-3.7) in adults; and 1.2 L (0.5-1.8) in children. At the lowest resistance a minimal flow rate of 30, 45, and 60 LPM was attained in 100%, 99%, and 96% of all patients. Volumes of 1.0, 1.5, and 2.0 L were attained by 85%, 57%, and 30% of the patients. At the highest resistance mean PIF(DPI) was 52 LPM (range 26-70) for all patients; 55 LPM (40-70) in adults; and 47 LPM (26-62) in children. Mean inspired V(DPI) was 1.5 L in all patients; 1.9 L (0.9-3.5) in adults and 1.1 L (0.5-2.3) in children. At the highest resistance, a minimal flow rate of 30, 45, and 60 LPM was attained in 99%, 80%, and 22% of all patients. Volumes of 1, 1.5, and 2 L were attained in 84%, 45%, and 23% of the patients. We defined ranges for inspiratory variables in a diverse CF population for a range of device resistances that bracket those of current DPIs. The recorded inspiratory patterns can be used on the bench to design and test new dry powder formulations and devices to target the largest proportion of the CF population.     

Multiple subcortical haemorrhages following lumbar metrizamide myelography

Summary The case is presented of a patient showing multiple subcortical haemorrhages after lumbar metrizamide myelography. This complication after intrathecally administered metrizamide contrast medium appears not to have been reported before. Several different possible explanations are proposed for the phenomena observed in this case.     

A unique case of bradycardia recognized by wearable technology as first presentation of complete heart block

Wearable technology has advanced significantly, and the proposed health benefits have been widely touted. Most of the discussion has been surrounding the identification and diagnosis of asymptomatic atrial fibrillation. However, the heart monitoring functions of the wearable technology can also identify other abnormalities as well. We present the first case of wearable technology identified bradycardia diagnosed as the primary presentation of complete heart block. Wearable technology has advanced significantly, but still poses questions regarding its use in screening for rare conditions. One remaining challenge is balancing the desire to screen for rare asymptomatic conditions without overburdening emergency departments with patients responding to alarms on their devices.     

Expression of yeast hexokinase in pancreatic beta cells of transgenic mice reduces blood glucose, enhances insulin secretion, and decreases diabetes.

It has been proposed that endogenous hexokinases of the pancreatic beta cell control the rate of glucose-stimulated insulin secretion and that genetic defects that reduce beta-cell hexokinase activity may lead to diabetes. To test these hypotheses, we have produced transgenic mice that have a 2-fold increase in hexokinase activity specific to the pancreatic beta cell. This increase was sufficient to significantly augment glucose-stimulated insulin secretion of isolated pancreatic islets, increase serum insulin levels in vivo, and lower the blood glucose levels of transgenic mice by 20-50% below control levels. Elevation of hexokinase activity also significantly reduced blood glucose levels of diabetic mice. These results confirm the role of beta-cell hexokinase activity in the regulation of insulin secretion and glucose homeostasis. They also provide strong support for the proposal that reductions in beta-cell hexokinase activity can produce diabetes.     

Initial improvements in lung function and bronchial hyperresponsiveness are maintained during 5 years of treatment with inhaled beclomethasone dipropionate and terbutaline.

OBJECTIVES: Treatment with inhaled corticosteroids reduces bronchial hyperresponsiveness and relieves airways obstruction in patients with asthma. Up to now, it is unknown whether initial improvements are maintained over a long period of time. Therefore, we assessed whether initial improvements in FEV(1), provocative concentration of histamine causing a 20% fall in FEV(1) (PC(20)), and peak expiratory flow (PEF) persist with a constant dose of inhaled corticosteroids. Furthermore, we investigated whether FEV(1), PC(20), PEF indexes, and symptom scores improve after increasing the dose of inhaled corticosteroids in patients who did not respond sufficiently to treatment with beclomethasone dipropionate (BDP), 800 microg/d. METHODS: Sixty-eight patients with bronchial hyperresponsiveness and airways obstruction completed a previous study on 3 years of treatment with terbutaline, 500 microg qid, and BDP, 200 microg qid. Fifty-eight of these patients participated in the current extension of another 2.5 years of follow-up. Every 6 months, FEV(1) and PC(20) were measured. Five patients dropped out of the study, one for pulmonary reasons. Forty-four patients continued treatment with BDP, 800 microg/d (BDP-800 group), and 9 patients received a higher dose of BDP (500 microg tid; BDP-1,500 group) after the first 3 years because of a rapid decline in FEV(1) (> 50 mL/yr) despite BDP treatment during the previous study period. RESULTS: After the initial improvement, the mean slope of individual regression lines for FEV(1), PC(20), and morning PEF were - 28 mL/yr, - 0.01 doubling concentrations per year, and 0.6 L/min/yr, respectively, in the BDP-800 group. In the BDP-1,500 group, there were no statistically significant improvements in FEV(1), PC(20), PEF indexes, and symptom scores after increasing the dose of BDP. CONCLUSIONS: We conclude that initial improvements in FEV(1), PC(20), and PEF are well preserved over 5 years in patients with obstructive airways diseases who are treated with terbutaline and BDP. In the patients who responded sufficiently to 800 microg/d of BDP, there was no accelerated decline in FEV(1) compared with the general population. Increasing the dose of BDP in a small group of patients with an accelerated fall in FEV(1) (initially treated with a moderate dose of BDP) resulted in no significant improvement in FEV(1), PC(20), PEF indexes, and symptom scores.     

Formoterol added to low-dose budesonide has no additional antiinflammatory effect in asthmatic patients

STUDY OBJECTIVE: Adding inhaled long-acting beta2-agonists to a low dose of inhaled corticosteroids (ICSs) results in better asthma control than increasing the dose of ICSs. An important, but as yet unresolved, question is whether this is due to an additional reduction of airway inflammation. DESIGN: Double-blind, parallel-group trial. PATIENTS: Forty asthma patients (FEV1, 50 to 90% predicted; provocative concentration of a substance [methacholine] causing a 20% fall in FEV1 of < 8 mg/mL; no ICSs in the last 4 weeks). INTERVENTIONS: Randomization to 8 weeks of treatment with 100 microg of budesonide bid plus placebo (BUD200) or 100 microg of budesonide bid plus 12 microg of formoterol (BUD200 + F). Then the dose of budesonide (BUD) was increased to 400 microg bid in both groups for another 8 weeks. Bronchial biopsy specimens were collected before, and after 8 and 16 weeks of treatment. Eosinophils (major basic protein [MBP]) and mast cells (tryptase) were analyzed by immunohistochemistry. RESULTS: BUD200 reduced the MBP staining (p = 0.008) and tryptase staining (p = 0.048) in the epithelium compared to baseline levels. There were no significant differences between the BUD200 and BUD200 + F groups. In both groups, increasing the dosage of BUD to 800 microg had no significant additional antiinflammatory effect. CONCLUSIONS: Our results demonstrate that BUD administered at a low dose has significant antiinflammatory effects in patients with mild asthma. No significant additional antiinflammatory effects could be demonstrated either by adding formoterol or by increasing the dose of BUD.     

Interactive effect of family history and environmental factors on respiratory tract-related morbidity in infancy

BACKGROUND: Family and environmental factors affect the development of respiratory morbidity. How these factors interact is unclear. OBJECTIVE: We sought to clarify the interactive effect of family history of asthma and environmental factors on the occurrence of respiratory morbidity. METHODS: Two hundred twenty-one infants with a positive family history of asthma (PFH) and 308 with a negative family history of asthma (NFH) were prenatally selected and followed until the age of 2 years. Exposure to environmental factors and the occurrence of respiratory morbidity were recorded. By using multiple logistic regression analysis, increased risk was expressed in odds ratios (ORs) adjusted for relevant covariables. RESULTS: Infants with a PFH had more respiratory morbidity than infants with an NFH. Adjusted ORs ranged from 1.7 (95% CI, 1.0-2.8) for expiratory wheezing to 4.9 (95% CI, 1.7-13.6) for croup. Parental smoking increased the OR of a PFH for wheezing ever (OR, 5.8 [95% CI, 2.5-13.8]) and attacks of wheezing (OR, 6.8 [95% CI, 2.7-16.9]), as did Der p 1 (OR, 10.2 [95% CI, 2.8-36.3] and OR, 7.1 [95% CI, 7.1-21.0], respectively). Exposure to both parental smoking and Der p 1 further increased this OR (OR, 30.8 [95%, CI, 6.9-137.2] and OR, 26.2 [95% CI, 5.9-115.6], respectively). Breast-feeding decreased the ORs of PFH for tonsillitis and acute otitis media: the increased ORs for these diagnoses in formula-fed infants with PFHs versus those with NFHs (OR, 9.2 [95% CI, 2.1-39.7] and OR, 2.9 [95% CI, 1.1-7.2], respectively) was attenuated in breast-fed infants (OR, 1.8 [95% CI, 0.8-3.8] and OR, 0.7 [95% CI, 0.4-1.3]). CONCLUSION: Parental smoking and Der p 1 increase the effect of a PFH on respiratory morbidity. Breast-feeding reduces this effect. CLINICAL IMPLICATIONS: Extra attention should be given to stimulate mothers to breast-feed their children in case they cannot stop smoking or taking sanitation measures.     

Undiagnosed patients and patients at risk for COPD in primary health care: early detection with the support of non-physicians

Given the increasingly heavy workload in the primary health care sector, the option of allocating activities involving the management of chronic diseases to non-physicians has recently come under scrutiny. The purpose of this study was to assess the feasibility of the support provided by non-physicians to general practitioners (GPs) in the early detection of chronic obstructive pulmonary disease (COPD). A convenience sample consisting of 231 patients [40-70 years; >10 pack years (number of packs of cigarettes smoked per day multiplied by the number of years the individual has smoked)] from eight general practices in the Maastricht region in the southern Netherlands, who consulted their GP for reasons unrelated to respiratory diseases, were assessed for their respiratory function. Prior to the first assessment, patients were interviewed about their medical history and symptoms. By taking the results of the lung function measurement as the starting point, the predictive value of medical history and symptoms in the identification of patients at risk for airflow obstruction or of COPD was assessed and compared with findings in the literature. Seventeen patients (7.4%) were diagnosed with COPD, 11 patients (4.8%) with asthma. In addition to age and moderate smoking history, breathlessness and a history of heavy smoking were identified as risk factors for airflow limitation and COPD. Early detection of COPD in primary health care by non-physicians is feasible and should be considered for middle aged, moderate and heavy smokers experiencing breathlessness.