American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 1997
Randomized Controlled Trial Clinical TrialEffect of regular salmeterol treatment on albuterol-induced bronchoprotection in mild asthma.
There is increasing evidence for the development of tolerance to the bronchoprotective effects of inhaled beta 2-agonists against bronchoconstrictor stimuli in asthma. With short-acting beta 2-agonists, this is more readily demonstrable using indirectly acting agents such as adenosine monophosphate (AMP), which may act via mast cell degranulation, than using methacholine (MCh), implying more rapid mast cell than smooth muscle desensitization. Desensitization may be greater with the long-acting beta 2-agonist, salmeterol, given its greater duration of receptor occupancy. ⋯ Mean MCh PC20 after albuterol decreased significantly after 2 wk of salmeterol treatment (mean 2.2 mg/ml before to 1.1 +/- 1.2 mg/ml after) compared with placebo (2.9 +/- 1.3 mg/ml before to 2.6 +/- 1.3 mg/ml after; p < 0.05), but this fell just short of statistical significance when analyzed as change in doubling dilutions (1.1 +/- 0.4 versus 0.18 +/- 0.4; p = NS). Mean PC20 to AMP was not significantly affected (mean 27.5 +/- 1.5 mg/ml prior to salmeterol treatment and 9.5 +/- 1.5 mg/ml after treatment; p = NS compared with placebo). Thus, regular salmeterol treatment led to loss of bronchoprotection by albuterol to MCh but not to AMP challenge, implying an absence of mast cell beta 2-adrenoceptor downregulation with regular salmeterol therapy.
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Am. J. Respir. Crit. Care Med. · Sep 1997
Clinical Trial Controlled Clinical TrialImpact of positive end-expiratory pressure on chest wall and lung pressure-volume curve in acute respiratory failure.
To investigate whether chest-wall mechanics could affect the total respiratory system pressure-volume (P-V) curve in patients with acute respiratory failure (ARF), and particularly the lower inflection point (LIP) of the curve, we drew the total respiratory system, lung, and chest-wall P-V curves (P-Vrs, P-VL, and P-VW, respectively) for 13 patients with ARF, using the supersyringe method together with the esophageal balloon technique. Measurements were randomly repeated at four different levels of positive end-expiratory pressure (PEEP) (0, 5, 10, 15 cm H2O) and from each P-V curve we derived starting compliance (Cstart), inflation compliance (Cinf), and end compliance (Cend). With PEEP of 0 cm H2O (ZEEP), an LIP on the P-Vrs curve was observed in all patients (7.5 +/- 3.9 cm H2O); in two patients an LIP was detected only on the P-VL curve (8.6 and 8.7 cm H2O, respectively); whereas in seven patients an LIP was observed only on the P-VW curve (3.4 +/- 1.1 cm H2O). ⋯ At high levels of PEEP, an upper inflection point (UIP) appeared on the P-Vrs and P-VL curves (11.7 +/- 4.9 cm H2O and 8.9 +/- 4.2 cm H2O above PEEP, respectively) suggesting alveolar overdistension. In general, PaO2 increased with PEEP (from 81.7 +/- 35.5 mm Hg on ZEEP to 120 +/- 43.8 mm Hg on PEEP 15 cm H2O, p < 0.002); however, the increase in PaO2 with PEEP was significant only in patients with an LIP on the P-VL curve (from 70.5 +/- 16.2 mm Hg to 117.5 +/- 50.7 mm Hg, p < 0.002), the changes in PaO2 in patients without an LIP on the P-VL curve not being significant (from 91.3 +/- 45.4 mm Hg to 122.2 +/- 41.1 mm Hg). We conclude that in ventilator-dependent patients with ARF: (1) the chest-wall mechanics can contribute to the LIP observed on the P-Vrs curve; (2) the improvement in PaO2 with PEEP is significant only in patients in whom LIP is on the lung P-V curve and not on the chest wall curve; (3) high levels of PEEP may overdistend the lung, as reflected by the appearance of a UIP; (4) measurement of P-Vrs alone may be misleading as a guide for setting the level of PEEP in some mechanically ventilated patients, at least in the supine position, although it helps to prevent excessive alveolar overdistension by indicating the inflection volume above which UIP may appear.
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Am. J. Respir. Crit. Care Med. · Sep 1997
Early detection of type III procollagen peptide in acute lung injury. Pathogenetic and prognostic significance.
The fibroproliferative reaction to acute lung injury may limit restoration of normal lung function and increase mortality in patients with acute lung injury. A biologic marker of collagen synthesis in the lung may be useful for studying the pathogenesis of acute lung injury and for identifying patients with acute lung injury who are at high risk for death and might benefit from new therapeutic modalities. Using an immunoassay, type III procollagen NH2 terminal peptide was measured in the pulmonary edema fluid of 44 patients with either acute lung injury or hydrostatic pulmonary edema (control group) within the first 24 h after endotracheal intubation for acute respiratory failure. ⋯ This evidence suggests that fibrosing alveolitis begins much earlier in the course of clinical acute lung injury than has previously been appreciated. In addition, the presence of an elevated level of procollagen III is an early predictor of poor outcome. Thus, elevation of procollagen III in pulmonary edema fluid may have both pathogenetic and prognostic significance in patients with acute lung injury.
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Am. J. Respir. Crit. Care Med. · Sep 1997
Chronic respiratory symptoms, skin test results, and lung function as predictors of peak flow variability.
We examined how chronic respiratory symptoms, reported in a questionnaire, and results of skin prick tests and spirometry predicted variability in peak expiratory flow (PEF) among 6-12-yr-old children (n = 1,854). After characterization with skin tests and spirometry, children were followed for 2-3 mo during the winter of 1993-1994. Peak expiratory flow was measured daily in the morning and evenings. ⋯ In conclusion, chronic respiratory symptoms reported in a questionnaire, spirometric lung function and skin prick test results among asthmatic children predicted variation in PEF measured during a 2-3 mo follow-up. The difference in morning PEF coefficient of variation (CV) between children with asthmatic symptoms and children with cough only was somewhat bigger in girls than in boys. The effect of atopy on morning PEF CV was somewhat bigger in young than in older children.