Nestor A. Molfino

Effect of low concentrations of ozone on inhaled allergen responses in asthmatic subjects

The relation between inhalation of ambient concentrations of ozone and airway reactivity to inhaled allergens may be important in asthma, since both agents can produce inflammatory changes in the airways. Seven asthmatic patients (mean age 40 [SD 13] years), with seasonal symptoms of asthma and positive skin tests for ragweed or grass, took part in a study to investigate whether exposure to low concentrations of ozone potentiates the airway allergic response. The patients were studied during 4 separate weeks in the winter. In each week there were 3 study days: on days 1 and 3 methacholine challenges were carried out; and on day 2 the subject received one of four combined challenges in a single-blind design--air breathing followed by inhalation of allergen diluent (placebo); ozone followed by inhalation of allergen diluent; air followed by allergen; or ozone followed by allergen. The ozone concentration was 0.12 ppm during 1 h of tidal breathing at rest, and allergens were inhaled until the forced expiratory volume in 1 s (FEV1) had fallen by 15% (PC15). There were no significant differences in baseline FEV1 after exposure to ozone but PC15 was significantly reduced when allergen was preceded by ozone inhalation: the mean PC15 after air was 0.013 (SD 0.017) mg/ml compared with 0.0056 (0.0062) mg/ml after ozone (p = 0.042). Thus, low ozone concentrations, similar to those commonly occurring in urban areas, can increase the bronchial responsiveness to allergen in atopic asthmatic subjects. This effect does not seem to be the result of changes in baseline airway function.

Respiratory arrest in near-fatal asthma

BACKGROUND AND METHODSnThe majority of asthma-related deaths occur outside the hospital, and therefore the exact factors leading to the terminal event are difficult to ascertain. To examine the mechanisms by which patients might die during acute exacerbations of asthma, we studied 10 such patients who arrived at the hospital in respiratory arrest or in whom it developed soon (within 20 minutes) after admission.nnnRESULTSnThe characteristics of the group were similar to those associated in the literature with a high risk of death from asthma, including a long history of the disease in young to middle-aged patients, previous life-threatening attacks or hospitalizations, delay in obtaining medical aid, and sudden onset of a rapidly progressive crisis. Extreme hypercapnia (mean [+/- SD] partial pressure of arterial carbon dioxide, 97.1 +/- 31.1 mm Hg) and acidosis (mean [+/- SD] pH, 7.01 +/- 0.11) were found before mechanical ventilation was begun, and four patients had hypokalemia on admission. Despite the severe respiratory acidosis, no patient had a serious cardiac arrhythmia during the resuscitation maneuvers or during hospitalization. We observed systemic hypertension and sinus tachycardia in eight patients, atrial fibrillation in one, and sinus bradycardia in another. In both patients with arrhythmia the heart reverted to sinus rhythm immediately after manual ventilation with 100 percent oxygen was begun. The median duration of mechanical ventilation was 12 hours, and all patients had normocapnia on discharge from the hospital.nnnCONCLUSIONSnWe conclude that at least in this group of patients, the near-fatal nature of the exacerbations was the result of severe asphyxia rather than cardiac arrhythmias. These results suggest that undertreatment rather than overtreatment may contribute to an increase in mortality from asthma.

Effect of Inhaled Furosemide in Acute Asthma

We assessed the acute bronchodilator effect of nebulized furosemide when added to conventional therapy of acute emergency department (ED) asthma. Using a double-blind design, 42 patients with acute asthma were randomized to receive 2.5 mg nebulized salbutamol and either 40 mg of nebulized furosemide or saline solution. We recorded clinical variables (respiratory rate, heart rate, and pulsus paradoxus) and peak expiratory flow rates (PEFR) before and 15 and 30 min after therapy. We found no significant difference in PEFR between salbutamol/furosemide and salbutamol/saline-treated patients 15 and 30 min following inhalation. Other endpoints were equally unaffected. However, when we examined separately those patients whose exacerbations were of relative short duration (< 8 hr), PEFR improved significantly more in the furosemide-treated group. At 15 min, PEFR increased by 82 +/- 48% in the furosemide group compared to 35 +/- 40% in the control group (p = 0.03), an effect that was also evident at 30 min when PEFR had increased by 113 +/- 49% in the furosemide group versus 61 +/- 35% in the control group (p = 0.014). Respiratory rate, heart rate, and pulsus paradoxus improved with no differences between the groups. The beneficial effect of furosemide was not evident in patients who reported more prolonged duration (> 8 hr) of asthmatic symptoms. The response to furosemide appeared to be unrelated to concomitant ED therapy with corticosteroids, to baseline pulmonary function, or to patient demographic variables. We conclude that furosemide may offer additive bronchodilator benefits in acute naturally occurring asthma of relative short duration.

Discriminating sputum-eosinophilic asthma: Accuracy of cutoffs in blood eosinophil measurements versus a composite index, ELEN

laboratory a priori deciding in a different way for the clinician on what the laboratory considers a ‘‘clinically relevant’’ positive threshold on the basis of limited and often subjectively collected data. Changes to this differential use of lower limits of quantitation will occur only when the requesting physician who orders IgE antibody analyses during a diagnostic workup of their patients requires that their clinical laboratory report uniform analytical sensitivity sanctioned by the manufacturer and regulators. As part of global harmonization of analytical methods, use of a uniform lower limit of quantitation is especially important for physicians who receive reports generated by different laboratories across the globe that use the same IgE antibody assay system. One goal of the International Standards Organization/Clinical Laboratory Standards Institute consensus guidance documents is the worldwide use of harmonized IgE antibody assay working ranges and limits of quantitation so that a report generated anywhere in the world will provide the same analytical data for interpretation by the clinician. Robert G. Hamilton, PhD, D.ABMLI