Michael T. Newhouse

The assessment and treatment of asthma: A conference report

The article published below is the result of the thoughtful workshop deliberations of many investigators interested in and very experienced in the assessment and treatment of asthma. As noted by them, the article is not intended to be a set of authoritative guidelines, but rather a presentation of the opinions of the interested individuals. Committees of the American Academy of Allergy and immunology are also currently addressing some of the points discussed here. I believe that our readers will be very interested in reading these thoughts about areas in which we all still have much to learn-Button Zweiman, MD, Editor.

Acute Response to Bronchodilator: An Imperfect Guide for Bronchodilator Therapy in Chronic Airflow Limitation

We conducted a four-period cross-over randomized trial in which we found that patients with chronic airflow limitation demonstrated symptomatic improvement with both inhaled albuterol and oral theophylline. The response, however, was not uniform. We therefore tested the ability of acute change in forced expired volume in one second (FEV1) following inhaled beta agonist to predict long-term symptomatic response to albuterol and theophylline. We found that the reproducibility of acute change in FEV1 over three repetitions was poor (intraclass correlation 0.17). Furthermore, the mean improvement FEV1 following inhaled albuterol across the three repetitions did not relate closely to symptomatic response to either albuterol or theophylline. We conclude that acute response to inhaled beta agonist is not useful for identifying patients with chronic airflow limitation who are likely to benefit from bronchodilator treatment.

Design and characteristics of a portable breath actuated, particle size selective medical aerosol inhaler

Abstract A new medical aerosol inhaler comprising a pressurized canister or metered dose inhaler (MDI), an aerosol holding chamber and a one-way valve system has been designed. Coordination of inhalation with actuation of the canister is no longer necessary as the valve ensures that aerosol is delivered only upon inspiration. The optimum chamber dimensions were found experimentally to be a cylinder approx. 11 cm in length by 3.5 cm diameter. It was deduced that the large particles from the MDI, which usually deposit in the upper airway during standard metered dose inhaler use, impacted in the holding chamber and the remainder evaporated to smaller size particles. These smaller particles (

Pulmonary Mucociliary Clearance in Cystic Fibrosis

Abstract Pulmonary clearance was examined by measurement of the rate of removal of a 99mTc-albumin aerosol (aerodynamic mass median diameter 3 μ) in 13 children with cystic fibrosis. Lung retention of radioactive label was monitored with a scintillation camera interfaced to a data-storage and retrieval system. The results were compared to those of nine normal adults. Overall lung retention was at all times greater in the normal subjects than in the patients (83.9 per cent at six hours after initial deposition vs. 59.6 per cent). The clearance curves of the patients had two exponentials with clearance half-times of 0.7 and 11.5 hours respectively. The mean curve for the normal subjects had a single exponential with half-times of 23.0 hours. In clinically stable patients with cystic fibrosis, clearance of inhaled aerosol from ciliated airways takes place at rapid rates, similar to those previously reported for mucociliary transport in normal adults.

Effect of TLV levels of SO2 and H2 SO4 on bronchial clearance in exercising man.

Pulmonary mucociliary function was assessed following exposure to industrial threshold limit values (TLV) of sulfur dioxide (5 ppm) SO2) and sulphuric acid mist (1 mg/m3 H2SO4). Bronchial clearance was measured in two sets of ten healthy exercising non-smoking adults under control and exposure conditions. A 99mTc-albumen saline aerosol (MMD 3 micrometer) was inhaled as a bolus in late inspiration under controlled conditions to produce reproducible deposition in large airways. Lung retention of radioactivity was quantified using a gamma camera and computer analysis. Clearance was significantly faster (P less than .05) on exposure to both SO2 and H2SO4 compared to control values. Maximum mid-expiratory flow rates (MMFR) were significantly reduced (P less than .01) on exposure to SO2 (mean decrease 8.5%), but only slightly reduced for H2SO4 (1.4%). The speeding in clearance was probably an irritant response in both cases. For SO2 the response appeared predominantly reflex, while H2SO4 showed evidence of a direct effect.

Response of asthmatic patients to fenoterol inhalation: a method of quantifying the airway bronchodilator dose.

A radiotracer technique is described which enables direct measurement of the dose and distribution of inhaled aerosol bronchodilator in man. The mean (±SD) amounts of the B2‐adrenergic agonist, fenoterol, administered to a group of 12 asthmatic subjects in a double‐blind randomized fashion were: placebo, 0 µg; low dose, 5.6 (± 1.2) µg; medium dose, 32.7 (±7.3) µg; and high dose, 127.5 (±29.2) µg, with a mean of 86.3% of the total subject dose being deposited in the lungs. The medium and high doses of fenoterol produced similar increases above baseline in forced expired volume in 1 sec (FEV1), maximum flow at 50% of vital capacity (Vmax 50), and maximum flow at 25% of vital capacity (Vmax 25). These increases were greater than those with placebo for the entire 4‐hr study (p < 0.01). The low dose of fenoterol was more effective than placebo in increasing FEV1, Vmax 50, and Vmax 25 above baseline values (p < 0.05), but not for the entire 4‐hr study. The high‐dose fenoterol caused palpitations and tremor in 3 of the 12 subjects, and the medium‐dose fenoterol caused palpitations in one of these subjects.

Lung defense mechanisms (second of two parts).

(Second of Two Parts) Macrophages The alveolar macrophage system has been extensively studied. Alveolar macrophages are responsible for the physical removal of inhaled particles although the major ...

Factors that affect the efficacy of inhaled corticosteroids for infants and young children.

Infants (0-1 years of age) and young children (1-3 years of age) are a unique subpopulation with regard to inhaled therapies. There are various anatomic, physiological, and emotional factors peculiar to this age group that present significant difficulties and challenges for aerosol delivery. Most studies of therapeutic aerosols that have been performed with patients of this age group, particularly recent studies with inhaled corticosteroids (ICSs), administered aerosols with relatively large particles (ie, >3 microm in mass median aerodynamic diameter). These drugs were designed for use in adults and older children and were administered with masks, which are frequently rejected by patients. Based on these studies, it was recently suggested that ICSs might not be as therapeutically effective in infants and young children as in adults. We review the reasons that large-particle corticosteroid aerosols are not likely to be effective in infants and young children. This patient population differs from adults in airway anatomy and physiology, as well as in behavior and adherence to therapy. We suggest that the benefit of ICSs in this age group requires further evaluation to determine whether better therapeutic outcomes might be achieved with smaller particles.

Review of optimal characteristics of face‐masks for valved‐holding chambers (VHCs)

Inhaled drugs are frequently given to infants and young children with a pressurized metered‐dose inhaler (pMDI) attached to a valved‐holding chamber (VHC) with face mask. In young children and infants who cannot breathe through a mouthpiece, the face mask serves as the interface between the patient and the VHC.

Sulfur dioxide and tracheobronchial clearance in man.

Tracheobronchial clearance was measured in nine healthy, nonsmoking adults. Technetium Tc 99m albumin aerosol (mass median diameter, 3 mu; geometric standard deviation, 1.6) was inhaled as a bolus under controlled conditions to achieve reproducible deposition in large airways. Each subject was studied in three seperate three-hour experiments: twice under control conditions and once exposed to 5 ppm sulfur dioxide (pollutant exposure after aerosol inhalation). Lung retention of activity was measured using a gamma camera interfaced to a data storage and retrieval system. The study showed that (1) Both deposition and clearance were highly reproducible in individuals in repeat control studies. (2) Acute exposure to 5 ppm sulfur dioxide had no significant effect (P greater than .05) on mucocillary clearance in resting healthy subjects, except perhaps for a small transient change (P=.05) after one hour. (3) Pulmonary function tests showed a decrease in maximal midexpiratory flow (P less than .01) but no other significant changes.