The impact of smoking on mechanical properties of the lungs in idiopathic pulmonary fibrosis and sarcoidosis.

Interstitial lung disease is characterized by interstitial inflammatory cell infiltration and fibrosis, a reduction in lung volumes, an increase in lung elastic recoil, and rapid shallow respirations. However, the alterations in lung volumes and elastic recoil as well as in breathing pattern are extremely variable, and the values are normal in a number of patients. In order to determine whether the effects of smoking could account for the variability in lung volumes and breathing pattern, we evaluated the elastic properties of the lung and the respiratory frequency at rest and during exercise in smokers and in nonsmokers with idiopathic pulmonary fibrosis (IPF) or with sarcoidosis. The volume-pressure curve in patients with IPF who smoked was positioned upwards and to the left when compared with that in nonsmokers. Conversely, the volume-pressure curve in patients with sarcoidosis who smoked was shifted downwards and to the right. In both conditions the respiratory rate while at rest and during exercise was greater in the group of patients who demonstrated the lower positioning of volume-pressure curves of the lungs (i.e., nonsmokers with IPF and smokers with sarcoidosis). We conclude that the impact of smoking may account, at least in part, for the variability in lung volume and volume-pressure characteristics of the lungs as well as the variability in respiratory rates in patients with interstitial lung disease.

111Indium-labeled neutrophil migration into the lungs of bleomycin-treated rabbits assessed noninvasively by external scintigraphy.

Factors controlling neutrophil migration into the lung are poorly understood, but their identification is important for our understanding of the pathogenesis of inflammatory lung diseases. Pulmonary inflammation is difficult to quantify, and neutrophils in tissues and BAL may not accurately represent cell migration. In this study, intravenously delivered pulses of rabbit neutrophils labeled with Indium-111 (111In-neutrophils) were used to monitor neutrophil migration into the lungs. Radioactivity quantified in the lung "region of interest" (ROI) of external gamma camera scintigrams recorded 24 h after intravenous 111In-neutrophil injection accurately reflected the actual neutrophil-associated lung tissue radioactivity. ROI radioactivity at 24 h also correlated closely with the percent of 111In-neutrophils that had migrated into lavageable air spaces, and this parameter therefore provided an index of total lung 111In-neutrophil migration. Using 24-h ROI radioactivity and percent of injected 111In-neutrophils recovered in BAL at 24 h as indices of neutrophil migration into the lung, it was found that intratracheal saline caused only a transient neutrophil migration, whereas 10 U/kg intratracheal bleomycin induced migration that persisted for as long as 3 wk. 111In-neutrophil migration into the lung, assessed by external scintigraphy, correlated with total neutrophils quantified in histologic sections (r = 0.71, p = 0.006). The data suggest that this approach will be valuable in investigating mechanisms controlling neutrophil migration in lung inflammation, and that 111In-neutrophil scintigraphy may provide a noninvasive index of total lung neutrophil load that might be useful in staging inflammation in patchy diseases such as idiopathic pulmonary fibrosis.

The intensity of chronic lung inflammation and fibrosis after bleomycin is directly related to the severity of acute injury.

Interstitial lung disease is thought to result from progression of an initial lung injury and alveolitis into a chronic inflammatory process that produces fibrosis. However, the relationship between the severity of the initial phase of acute injury and alveolitis and the amount of subsequent chronic inflammation and fibrosis remains unclear. We induced a wide spectrum of acute lung injury in rabbits by using various amounts of intratracheal bleomycin (5 or 10 U/kg) with and without oxygen supplementation (100% O2 for 2 min). The arterial oxygen tension on Day 12 after the bleomycin correlated with the extent of acute lung injury, as well as with the amount of chronic inflammation and fibrosis present on Day 56, as determined by physiologic parameters (lung volume, DLCO/VA, and PO2), and morphometry (volume proportions abnormal parenchyma made up of intra-alveolar macrophages, intra-alveolar granulocytes, abnormal alveoli, abnormal airways, fibrosis, consolidation, and honeycombing). We conclude that in bleomycin-induced interstitial lung disease in the rabbit, there is a direct relationship between the severity of acute lung injury after intratracheal bleomycin and the amount of subsequent chronic inflammation and fibrosis. This suggests that the mechanisms regulating the development of fibrosis are directly influenced by the extent of initial injury.

The effect of topical ophthalmic instillation of timolol and betaxolol on lung function in asthmatic subjects.

The propensity of systemic beta-adrenergic blockers to cause bronchoconstriction in patients with reactive airway disease is well recognized. A study was carried out to determine the prevalence of sensitivity to ophthalmic timolol in 24 asthmatic subjects at our institution and to determine the effect of ophthalmic betaxolol, a cardioselective beta-blocker efficacious in the treatment of glaucoma, in 8 subjects who were timolol-sensitive. Subjects received topical timolol 0.5%; ventilatory function, blood pressure, and heart rate were monitored over a 90-min period. The mean FEV1 fell from 2.47 to 1.93 L by 30 min after drug treatment to a minimal value of 1.86 L (-27.8%). There was a corresponding fall in FVC from 3.68 to 3.09 L by 30 min with a minimal value of 3.00 L(-20.7%). FEV1/FVC ratio also fell from 66.9 to 61.0% by 30 min, reaching a minimum of 60.0%. In 14 subjects (58.3%), the fall in FEV1 was greater than or equal to 20%, with a mean fall of 38.7% by 30 min and a maximal fall of 44.9%. The severity of timolol-sensitivity correlated with the extent of reduction in baseline percent predicted FEV1 and FVC and with exercise-induced bronchospasm. In addition, the administration of timolol reduced the bronchodilator response to below the pretimolol value. In 8 of the timolol-sensitive patients who underwent a double-blind crossover challenge with ocular instillation of betaxolol 1% and saline, betaxolol was well-tolerated and did not affect ventilatory function over a 4-h observation period. In addition, it did not prevent the FEV1 response to inhaled bronchodilator.(ABSTRACT TRUNCATED AT 250 WORDS)