IMPEDANCE MEASUREMENT DURING AIR AND HELIUM-OXYGEN BREATHING BEFORE AND AFTER SALBUTAMOL IN COPD PATIENTS

1. The forced oscillation technique is an effort-independent method used to characterize the mechanical impedance of the respiratory system. To support the hypothesis that non-invasive partitioning of total pulmonary resistance is possible by this technique, impedance was measured during air breathing and after equilibration with a mixture of 80% helium (He) and 20% oxygen (O2) in 21 chronic obstructive pulmonary disease (COPD) patients by means of a forced pseudo-random noise pressure signal over a frequency spectrum from 4 to 52 Hz. Furthermore, during inhalation of both gas mixtures impedance was determined before and after inhalation of 0.400 mg Salbutamol. 2. He + O2 breathing caused less negative frequency dependence of resistance and a significant decrease in reactance over the range 16-52 Hz. Inhalation of Salbutamol caused a marked increase in reactance values over the range 8-40 Hz. However after equilibration with the He + O2 mixture, Salbutamol caused a significant decrease in resistance and a significant increase in reactance at all frequencies. 3. The results during He + O2 breathing are in accordance with a partitioning of airways resistance into central and peripheral components. The decrease in reactance during He + O2 can be explained by a density dependent decrease in inductive reactance. By comparing the impedance data during air and He + O2 breathing, it can be concluded that a distribution of pulmonary resistance with minimal losses in the larger airways is more sensitive for detecting changes in the peripheral airways in COPD patients.     

Effects of aspirin on nasal responses in atopic subjects

Preliminary experiments indicated that solutions of aspirin (ASA) in buffered saline, pH 7.35, did not significantly change nasal airways resistance (NAR) when 0.1 ml of solution containing 22.5 mg (or less) per deciliter was sprayed into each nostril. Subsequently it was shown that this quantity of ASA administered intranasally did not significantly change NAR responses 15 min later to intranasal administration of increasing concentrations of histamine, methacholine, or an irritant (NH₃ gas). However, the same atopic subjects demonstrated significantly decreased responses to intranasal challenge with short ragweed extract (SRW) after intranasal ASA. In addition, prior oral administration of ASA, Na salicylate, and indomethacin significantly inhibited nasal challenge responses to SRW in sensitive subjects under controlled conditions.     

Assessing Metered-Dose Inhaler Technique: Comparison of Observation vs. Patient Self-Report

The purpose of this study was to develop and determine the validity of a patient-completed questionnaire that assesses metered-dose inhaler (MDI) technique. Self-reported MDI technique was compared to observed technique. The questionnaire included nine steps for MDI use, with two to three response choices for each step. A total of 159 patients were studied. Direct observation revealed that greater than 82% of patients exhibited inadequate technique (more than two out of nine steps incorrect). The mean percentage agreement between the questionnaire and observation was 77.4%. Questionnaire results where in higher agreement with observation when patients performed correct MDI technique.     

Nitrogen dead space in heavy smokers aged 44–58 years

Summary. Functional and alveolar dead spaces for nitrogen (V_df and V_dalv) were calculated in a population of 20 male and 20 female heavy smokers and compared to data from static and forced spirometry (functional residual capacity [FRC], residual volume [RV], lung clearance index [LCI] and volume of trapped gas [VTG]) obtained with the same multiple-breath nitrogen wash-out as the dead spaces, and to variables considered sensitive to small airways disease measured with a single-breath nitrogen elimination (closing volume in per cent of vital capacity [CV%], closing capacity in per cent of total lung capacity [CC%] and slope index [SI]). Both nitrogen dead spaces increased with tidal volume in smokers as well as in healthy non-smokers. The majority of smokers were outside the predicted mean+2 SD for VTG (75%), CC and V_Dalv (70%) and SI (65%). The following variables were less sensitive for disclosing abnormality: CV (55%), RV (53%), LCI (38%) and forced expired volume in the first second (FEV₁, 33%). If high sensitivity is considered preferable in epidemiological studies, the nitrogen dead spaces are equally as sensitive as the better of earlier described tests, and significantly superior to LCI and FEV₁. Being tests that measure alveolar distribution of inhaled gas, they are probably sensitive to small airways disease.     

Protective effect by UCB JO28 against histamine and methacholine induced bronchial hyperreactivity

Summary UCB JO28 ([2-[2-[4-(diphenylmethylene)-l-piperidinyl] ethoxy] ethoxy] acetic acid, hydrochloride) is derived from diphenylmethylene piperidine. Animal experiments have shown that it has spasmolytic properties for smooth muscle, particularly in the bronchi, as well as anti-Hl, anticholinergic and anti-serotonin activities. The degree of protection by JO28 against histamine and methacholine-induced bronchospasm has been investigated in 20 asthmatic patients with serious airways hyper-reactivity. Protection against histamine-induced bronchospasm was almost complete in 11 out of 12 patients, whereas protection against methacholine-induced bronchospasm, although clearly present in seven of eight patients, was less marked.     

Adenoviral infection inhibits allergic airways inflammation in mice

BACKGROUND: Recent epidemiological studies have suggested that exposure to certain viruses and bacteria influences the development of allergy and allergic diseases, such as asthma. However, there is a paucity of experimental evidence examining the consequences of concurrent exposure to allergen and infectious agents, and the potential mechanisms by which allergic disease might be averted as a result. OBJECTIVE: To model this situation experimentally, we investigated whether a virally induced immune response, elicited by a replication-deficient human type 5 adenovirus (RDA) administered at a site distant from the airways, could inhibit ovalbumin (OVA)-induced airways eosinophilic inflammation. METHODS: C57BL/6 mice were infected intramuscularly with RDA 16h prior to intraperitoneal OVA sensitization. Cellular and cytokine responses in the lung/airways were examined after an OVA aerosol challenge. RESULTS: RDA infection significantly inhibited the inflammatory response in the lung tissue after antigen challenge. In the bronchoalveolar lavage (BAL), total cell number, eosinophils and lymphocytes were decreased by 70, 85 and 65%, respectively, after antigen challenge in RDA-treated, compared with untreated, mice. RDA infection had no effect on IgE synthesis. The levels of IL-5, IL-4 and IFNgamma in the BAL after antigen challenge were significantly lower in RDA-treated mice. In vitro production of cytokines by splenocytes in response to OVA restimulation revealed a shift from IL-4 in sensitized, PBS-treated mice, to IFNgamma in sensitized mice treated with RDA. Flow cytometric analysis revealed that RDA infection increased the proportion of CD8 T cells in the BAL; this change in T-cell subsets was accompanied by an increase in both CD4 and CD8 T cells positive for intracellular IFNgamma. Inhibition of antigen-induced airways inflammation was IFNgamma-dependent but did not require IL-12, as RDA-treatment inhibited airways inflammation in IL-12 but not IFNgamma knock-out mice. CONCLUSION: This study demonstrates that an immune response against a replication-deficient adenovirus during the initial exposure to OVA inhibits the development of airways inflammation after antigen aerosol challenge.     

Oropharyngeal flora as a source of bacteria colonizing the lower airways in patients on artificial ventilation

During 1 year 27 patients admitted to the respiratory intensive care unit were monitored bacteriologically for a minimum of 10 days (mean: 26.7 days). Oropharyngeal swabs and tracheal aspirates were qualitatively and semi-quantitatively cultured twice weekly. A correlation between oropharyngeal and tracheal flora was found: once a bacterial species colonized the oropharyngeal cavity in high numbers, the identical microorganism was frequently isolated (>50%) from the lower respiratory tract. Six of the 27 patients acquired an infection of the lower airways in the respiratory intensive care unit. The bacteria involved belonged to the patients oropharyngeal flora: S. aureus, Enterobacteriaceae and Pseudomonadaceae. As a result of this study showing the oropharynx to be the source of lower airway colonization/infection, a policy for infection prevention has been outlined. This policy is based on the concept of source elimination by means of oropharyngeal decontamination.     

Pharmacokinetics of a microcrystalline theophylline preparation in patients with chronic obstructive airways disease

Summary Plasma theophylline concentrations have been measured in 9 patients with chronic obstructive airways disease following the oral administration of a microcrystalline theophylline preparation. Some measurements of FEV₁ were also made. Four patients were given 375 mg as a single dose and then subsequently 375 mg stat and 125 mg 4 times daily for 3 days, (Group I). A further 5 patients took 250 mg as a single dose and then 250 mg 4 times daily for 3 days, (Group II). In both groups, following the single dose and again after the last dose of chronic administration, blood samples were obtained at frequent intervals up to 24 h for plasma drug estimation. During the 3-day course, blood samples were drawn before and 2 h after each morning dose. In Group I patients, substantial plasma theophylline concentrations were seen only after the loading dose. Thereafter, the mean concentrations before or 2 h after the morning doese were always less than 4.0 µg/ml. Trough concentrations were usually below 2.0 µg/ml. In contrast patients in Group II achieved substantially higher plasma theophylline concentrations, with mean peak concentrations always 10 µg/ml or greater, and trough concentrations greater than 5 µg/ml on at least one occasion in every subject. The elimination half-lives after chronic administration in both groups were not significantly different from those obtained after single doses. Mean drug accumulation, measured as AUC_ss/AUC₁, was 0.87±0.07 in Group I and 0.72±0.14 in Group II, indicating that accumulation had not occurred with either regimen. The mean increase in FEV₁ 2 h after the administration of a single dose was 19.2% after 375 mg and 16.7% after 250 mg. These results indicate that the recommended dosage regimen for microcrystalline theophylline preparation (375 mg stat and 125 mg 4 times daily) produces inadequate plasma theophylline concentrations: 250 mg 4 times daily would appear to be likely to result in satisfactory theophylline levels in more patients.