The effect of transfusion on pulmonary function in patients with thalassemia major

Pulmonary involvement has been documented in thalassemia major (TM). We studied 12 patients with TM before and 24 hr after transfusion to evaluate the effect of transfusion on baseline lung function. Personal and family histories of respiratory illnesses were obtained by a questionnaire. Spirometry and carbon monoxide diffusion capacity (KCO) measurements were made. Blood gases (P, and S,) were determined on arterialized samples. Baseline expiratory volumes and flows were within normal range in all patients. Transfusion resulted in a significant reduction of forced expiratory volume in 1 sec (FEV₁) and forced expiratory flow between 25 and 75% vital capacity (FEF_25–75%). In two subgroups of patients identified by the questionnaire, those with no history of airway disease had normal baseline flows and no posttransfusion changes; those with history of airway obstruction had lower pretransfusion flows and significantly decreased posttransfusion FEV₁ and FEF_25–75%. The mean pretransfusion KCO value of 80% predicted for the whole group, significantly increased after transfusion (P < 0.05). Blood gases also significantly increased after transfusion (P < 0.05). When tested for the spirometric response to albuterol, patients with a history of asthma had a slightly greater increase in FEV₁ and FEF_25–75% than those who had never had asthma. We conclude that in our small study group, transfusion resulted in improved gas exchange and lung perfusion. The effect on flow limitation evident in some patients could, in part, be related to a preexisting bronchial hyperreactivity. Accurate evaluation of pulmonary function and of bronchial reactivity is advisable for patients with TM. Pediatr Pulmonol. 1994;18:139–143. © 1994 Wiley-Liss, Inc.     

Airway dysfunction in patients with Parkinson's disease

To investigate pulmonary function abnormalities in Parkinson's disease (PD), we obtained maximal inspiratory and expiratory flow-volume curves in 63 patients (59 under treatment) with different stages of the disease, not filtered for respiratory symptoms. PD severity was evaluated by the Unified PD Rating Scale, the Webster's scale, and Hoehn and Yahr staging. Patients with more severe PD had lower percentage forced vital capacity (FVC%), and peak inspiratory and expiratory flows. Those with fluctuations and/or dyskinesias had lower FVC% and percentage forced expiratory flow volume in 1 sec (FEV₁%). There were a number of weak but significant correlations between PD scales and spirographic parameters. Thirty one patients (49.2%) had pathological flow-volume curves. The clinical profile and the duration of the disease did not influence the pattern of the curve. Physiologic evidence of upper airway obstruction was observed in 3 cases. A spirometric restrictive ventilatory defect (FEV₁/FVC higher than or equal to 80%) was observed in 54 patients (85%), while generalized airway obstruction was present only in one nonsmoker. We conclude that abnormal flow-volume loop contour is a frequent finding in PD. This probably reflects involvement of the upper airway musculature, that in some patients can produce upper airway obstruction. Generalized airflow limitation is not an important characteristic of PD. By contrast, a restrictive spirometric defect, probably due to incoordinated expiratory effort or abnormally low chest wall compliance, is the main spirometric finding in these patients. Offprint requests to: J. L. Izquierdo-Alonso     

Exhaled Nitric Oxide and Exercise-Induced Bronchospasm Assessed by FEV1, FEF25 − 75% in Childhood Asthma

The relationship between exhaled nitric oxide (eNO) and bronchial hyperresponsiveness (BHR) should be clarified. The aim of this study was to determine the relationship between eNO and exercise-induced bronchospasm (EIB) by estimation of the each lung parameter in asthmatic children who performed a bicycle ergometer exercise test. Twenty children with asthma were recruited. eNO concentration was examined by the recommended online method. To evaluate BHR, an exercise stress test was performed on a bicycle ergometer. The mean baseline eNO value was significantly correlated with the mean maximum % fall in forced expiratory volume in 1 second (FEV₁), forced expiratory flow between 25% and 75% (FEF25-75%) after exercise (r = 0.53, r = 0.65, respectively). eNO in the EIB-positive group was significantly higher than that in the EIB-negative group by assessing FEV₁, FEF_25?75% (p < 0.005, p = 0.005). We demonstrated that the most important lung parameter assessed the occurrence of EIB by a bicycle ergometer exercise test was not only FEV₁ but FEF_25?75%, which significantly correlated with eNO. This suggests that not only FEV₁ but FEF_25?75% can be used to evaluate the correlations between BHR (EIB) and airway inflammation (eNO) in asthmatic children. A low eNO is useful for a negative predictor for EIB.     

Association between increased small airway obstruction and asbestos exposure in patients with asbestosis

Background

Asbestos exposure may cause asbestos‐related lung diseases including asbestosis, pleural abnormalities and malignancies. The role of asbestos exposure in the development of small airway obstruction remains controversial. Anatomic and physiologic small airway abnormalities may develop as part of the pathophysiologic process of asbestosis. We hypothesized that inhalation of asbestos may induce small airway defects in addition to asbestosis and pleural abnormalities.

Methods

In total, 281 patients with newly diagnosed asbestosis were evaluated. Clinical data were collected from the patients' medical charts. The patients were classified into various stages according to their chest X‐ray findings using the International Labour Organization classification. Pulmonary function was evaluated by plethysmography and the forced oscillation technique.

Results

Expiratory flow, including the predicted values of the maximum expiratory flow between 25% and 50% of the forced vital capacity (MEF_25‐50), was significantly lower in the different stages of asbestosis. Accordingly, the predicted percentage of R₅–R₂₀ was significantly higher with increasing stages of asbestosis. Furthermore, the duration of exposure to asbestos was significantly associated with the forced expiratory volume in the first second (FEV₁)/forced vital capacity (FVC) ratio and the predicted percentage of MEF₂₅ or MEF₅₀ according to the regression analysis in non‐smoking patients with asbestosis. The predicted percentage of FEV₁ or the FEV₁/FVC ratio was significantly lower and the predicted percentage of R₅–R₂₀ was significantly higher in smokers than non‐smokers.

Conclusions

The patients with asbestosis have small airway obstructive defects that are significantly associated with asbestos exposure.     

Inspiratory flow limitation in children with bronchopulmonary dysplasia

The objective of this study was to compare pulmonary function tests of children with bronchopulmonary dysplasia (BPD) and asthma, and to evaluate children with BPD for evidence of upper airway obstruction. This is a case-control retrospective study of pulmonary function tests (PFTs) of 11 children with BPD between 5 and 8 years of age who were followed by pediatric pulmonologists, and of 32 age- and height-matched children with asthma. The median forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and peak expiratory flow (PEF) were significantly lower in the BPD group (0.86 L, 0.79 L, 120 L/min) than in the asthmatic group (1.34 L, 1.21 L, 155 L/min; P = 0.002, P = 0.007, P = 0.004, respectively). Both groups were equally hyperinflated (median thoracic gas volume 155% of predicted values in the BPD compared to 152% predicted in the asthma group; P = 0.67), and both groups showed decreases in air-trapping after a bronchodilator. The ratios of forced expiratory flow at 50% of the FVC to forced inspiratory flow at 50% of the FVC (FEF_50%/FIF_50%) and FEV₁ to PEF (FEV₁/PEF) were used to assess upper airway obstruction and were higher in children with BPD than asthma (P = 0.0001 and P = 0.035, respectively). We conclude that pulmonary function of children with BPD who are still symptomatic after 5 years of age is different from age-matched children with asthma, and the children with BPD demonstrate significant inspiratory flow limitations. Pediatr Pulmonol. 1998;26:167–172. © 1998 Wiley-Liss, Inc.     

Airway function tests and vocal cord paralysis in lung transplant recipients

Maximum expiratory and inspiratory flow-volume (MEFV, MIFV) curves, specific airway conductance (sG_aw), and flexible fiberoptic laryngoscopy were examined in 8 pediatric lung transplant recipients with vocal cord paralysis (VCP). Six were heart-lung (H-L) and 2 double-lung (D-L) recipients, 7 had left VCP, and 1 had right VCP. Based on the pulmonary function tests (PFT), 2 subgroups could be distinguished in the 8 recipients with VCP. Group A (5/8 recipients; mean age, 13 ± 3.4 years; mean height, 144.3 ± 12.3 cm) had significantly reduced specific airway conductance (sG_aw; < 2 SD from predicted) and normal MEF₂₅, MEF₅₀, peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV₁), and %FEV₁/forced vital capacity (FVC); this pattern suggested variable extrathoracic airway obstruction. PIF was normal in 4/5 and reduced in 1/5 of these recipients. Group B (3/8 recipients with VCP; mean age, 17 ± 2.4 years; mean height, 156.3 ± 12.0 cm) had significantly reduced sG_aw, MEF₂₅, MEF₅₀, PEF, FEV₁, and %FEV₁/FVC, implying primarily small airway obstruction. These recipients had bronchiolitis obliterans. The results suggest that a pattern of reduced sG_aw and normal MEFs, PEF, FEV₁, and PIF should raise the possibility of VCP in patients after lung transplantation. sG_aw is more sensitive than PIF and PEF in identifying airway obstruction due to VCP, and should be routinely included in the follow-up evaluation of lung transplant recipients. Pediatr Pulmonol. 1997; 23:87–94 . © 1997 Wiley-Liss, Inc.     

Improvement of “irreversible” airway obstruction by thiazinamium (Multergan®)

Thiazinamium (Multergan®, 50 mg intramuscularly) improved lung function (forced expiratory volume in one second [FEV_1.0]; forced vital capacity [FVC]) within one hour after injection in 11 men (average age 66.4 years) with chronic cough, phlegm, and dyspnea, and with severe ventilatory function loss (average FEV_1.0, 42.5% of predicted values; average FVC, 64.6%) due to prolonged exposure (≥28 years) to dust of soft hemp in industry. The increase of FEV_1.0 and of FVC after thiazinamium was significantly greater than that observed after isoproterenol inhalation in the same subjects. The acute effect of thiazinamium, which lasted at least six hours, was maintained over a one-month period of daily injections. Oral administration of 200 mg thiazinamium had little effect on FEV_1.0 and FVC. The results suggest that "irreversible" airway obstruction may be more amenable to drug treatment than is often thought.     

Cold Air and Exercise Challenge—Influence of Minute Ventilation

Exercises testing and cold air challenges are frequently used to assess airway hyperresponsiveness (AHR), but different goals are set for the two tests. We, therefore, wished to determine whether cold air and exercise challenge testing yielded similar responses and if any differences were due to differences in the maximum minute ventilation achieved.

Twenty asthmatic subjects each performed a cold air (CACh) and an exercise (EXCh) challenge. Baseline forced expiratory volume in one second (FEV₁) was recorded immediately pre-challenge and then serially for at least 10 minutes post-challenge. The maximum minute ventilation achieved was recorded. In the subjects who had at least a decrease in FEV₁ of 15% in response to the first CACh, a second CACh was performed, but at the maximum minute ventilation achieved during EXCh.

Eleven subjects after CACh and four after EXCh had a greater than 15% decrease in FEV₁ (p = 0.05). The median decrease in FEV₁ was greater following the CACh (16.7%[25th to 75th percentile 10.4 to 19.9]) than the EXCh (6.9%[25th to 75th percentile 4.3 to 14.6]); (p = 0.0004). The median maximum minute ventilation achieved was greater with the CACh (89[66–141] L/min) than with the EXCh (61(40 to 102)L/min); (p < 0.0001). Only one of seven subjects who had previously responded to the CACh had a 15% decrease in FEV₁ when the CACh was repeated at the same maximum minute ventilation achieved during EXCh (p = 0.007).

In conclusion, cold air and exercise challenges do not produce the same response. Our results highlight than an explanation is the differences in the maximum-minimum ventilation achieved.     

A restrictive ventilatory pattern is common in patients with univentricular heart after Fontan palliation and associated with a reduced exercise capacity and quality of life

Aim: The Fontan circulation is highly dependent on ventilation, improving pulmonary blood flow and cardiac output. A reduced ventilatory function is reported in these patients. The extent of this impairment and its relation to exercise capacity and qual‐ ity of life is unknown and objective of this study.
Methods: This multicenter retrospective/cross‐sectional study included 232 patients (140 females, age 25.6 ± 10.8 years) after Fontan palliation (19.8% atrioventricular connection; 20.3% atriopulmonary connection; 59.9% total cavopulmonary connec‐ tion). Resting spirometry, cardiopulmonary exercise tests, and quality‐of‐life assess‐ ment (SF‐36 questionnaire) were performed between 2003 and 2015.
Results: Overall, mean forced expiratory volume in one second (FEV₁) was 74.7 ± 17.8%predicted (%pred). In 59.5% of the patients, FEV₁ was <80%pred., and all of these patients had FEV₁/forced vital capacity (FVC) > 80%, suggestive of a restric‐ tive ventilatory pattern. Reduced FEV₁ was associated with a reduced peakVO₂ of 67.0 ± 17.6%pred. (r = 0.43, P < .0001), even if analyzed together with possible con‐ founding factors (sex, BMI, age, years after palliation, number of interventions, sco‐ liosis, diaphragmatic paralysis). Synergistically to exercise capacity, FEV₁ was associated to quality of life in terms of physical component summary (r = 0.30, P = .002), physical functioning (r = 0.25, P = .008), bodily pain (r = 0.22, P = .02), and general health (r = 0.16, P = .024). Lower FEV₁ was associated with diaphragmatic paralysis (P = .001), scoliosis (P = .001), higher number of interventions (P = .002), and lower BMI (P = .01). No correlation was found to ventricular morphology, type of surgeries, or other perioperative/long‐term complications.
Conclusions: This study shows that the common restrictive ventilatory pattern in Fontan patients is associated with lower exercise capacity and quality of life. Risk factors are diaphragmatic paralysis, scoliosis, a high total number of interventions and low BMI.     

Comparison of central and peripheral airway involvement before and during methacholine, mannitol and eucapnic hyperventilation challenges in mild asthmatics

Introduction: Testing for airway hyperresponsiveness with indirect stimuli as exercise or mannitol has been proposed to better reflect underlying airway inflammation, as compared with methacholine (MCh), believed to act directly on airway smooth muscle cells. Objective: To investigate whether different direct and indirect stimuli induces different patterns of obstruction, recorded as central and peripheral resistance, and to see whether baseline resistance could predict a positive response to direct or indirect provocation. Methods: Thirty‐four mild asthmatics and 15 controls underwent MCh, mannitol and eucapnic voluntary hyperventilation (EVH) challenge tests. The response was evaluated with spirometry and impulse oscillometry (IOS). Results: Twenty‐three out of 34 asthmatics were positive to either EVH (22) or mannitol (13). Those positive to mannitol had a significant increased baseline value of IOS parameters such as ΔR5‐R20 and AX. Twelve of the asthmatics had a 10% fall or more in forced expiratory volume in 1 s (FEV₁) in all three challenge tests. However, the response pattern measured by IOS did not differ between the tests. When the limit for a positive mannitol provocation was set to 10% fall in FEV₁, 16 out of 19 mannitol‐positive patients were also positive to EVH. Conclusion: Even in mild asthmatics, a substantial number had a positive indirect test. Mannitol FEV₁ provocative dose to decrease FEV₁ by 10% from baseline (PD10) was closely associated to EVH10%. No difference in bronchoconstrictive pattern could be seen between the different provocation tests, but those positive to mannitol had more peripheral airway involvement at baseline. This supports the idea that peripheral airway involvement is an important predictor of asthma airway reactivity. Please cite this paper as: Aronsson D, Tufvesson E, Bjermer L. Comparison of central and peripheral airway involvement before and during methacholine, mannitol and eucapnic hyperventilation challenges in mild asthmatics. Clin Respir J 2011; 5: 10–18.     

Resting Physiological Correlates of Reduced Exercise Capacity in Smokers with Mild Airway Obstruction

Smokers with minor spirometric abnormalities can experience persistent activity-related dyspnea and exercise intolerance. Additional resting tests can expose heterogeneous physiological abnormalities, but their relevance and association with clinical outcomes remain uncertain. Subjects included sixty-two smokers (≥20 pack-years), with cough and/or dyspnea and minor airway obstruction [forced expiratory volume in one-second (FEV₁) ≥80% predicted and >5th percentile lower limit of normal (LLN) (i.e., z-score >?1.64) using the 2012-Global Lung Function Initiative equations]. They underwent spirometry, plethysmography, oscillometry, single-breath nitrogen washout, and symptom-limited incremental cycle exercise tests. Thirty-two age-matched nonsmoking controls were also studied. Thirty-three (53%) of smokers had chronic obstructive pulmonary disease by LLN criteria. In smokers [n = 62; age 65 ± 11 years; smoking history 43 ± 19 pack-years; post-bronchodilator FEV₁ z-score ?0.60 ± 0.72 and FEV₁/FVC z-score ?1.56 ± 0.87 (mean ± SD)] versus controls, peak oxygen uptake (?VO₂) was 21 ± 7 vs. 32 ± 9 ml/kg/min, and dyspnea/?VO₂ slopes were elevated (both p < 0.0001). Smokers had evidence of peripheral airway dysfunction and maldistribution of ventilation when compared to controls. In smokers versus controls: lung diffusing capacity for carbon monoxide (D_LCO) was 85 ± 22 vs. 105 ± 17% predicted, and residual volume (RV)/total lung capacity (TLC) was 36 ± 8 vs. 31 ± 6% (both p < 0.01). The strongest correlates of peak ?VO₂ were D_LCO% predicted (r = 0.487, p < 0.0005) and RV/TLC% (r = ?0.389, p = 0.002). D_LCO% predicted was also the strongest correlate of dyspnea/?VO₂ slope (r = ?0.352, p = 0.005). In smokers with mild airway obstruction, associations between resting tests of mechanics and pulmonary gas exchange and exercise performance parameters were weak, albeit consistent. Among these, DLCO showed the strongest association with important outcomes such as dyspnea and exercise intolerance measured during standardized incremental exercise tests.     

Longitudinal follow-up of lung function from childhood to adolescence in prematurely born patients with neonatal chronic lung disease

We investigated whether early lung function abnormalities in prematurely born children with a history of chronic lung disease improve in late childhood and adolescence. We performed a prospective, longitudinal evaluations of pulmonary function over an 8 year period. In seventeen patients from the age (mean ± SD) of 8.2 ± 1.2 years to the age of 15.1 ± 1.6 years. They had been born at 29.1 ± 1.9 weeks of gestation, with a birthweight of 1120 ± 190 g, and they had received supplemental oxygen, with or without mechanical ventilation, for 40.4 ± 23.8 days during the neonatal period. They all had radiographic evidence of chronic lung disease at 4 weeks of age. Annual measurements of lung volumes using the helium dilution technique, and of airway function with spirometry and maximal expiratory flow-volume curves over a 5 to 8 year period, were obtained. The results indicated that total lung capacity (TLC) and vital capacity (VC) were within the predicted normal range in all patients and increased over time. In contrast, the initially abnormal residual volume (RV) and RV/TLC ratio decreased over time, suggesting gradual resolution of air-trapping. The peak expiratory flow rate (PEFR), forced expiratory volume in 1 second (FEV₁), and the ratio FEV₁/FVC remained at or above the predicted normal range in all patients. FEF_25–75, FEF₅₀, and FEF₇₅ were within normal limits in eight patients and abnormally low (more than 2 SD below the predicted normal value) in the remaining nine patients, indicating small airway obstruction. Eight of the nine patients with lower airway obstruction showed significant response to inhaled bronchodilator, and four responded to a histamine challenge. None of the eight patients with normal airway function responded to histamine, but four responded to bronchodilators. The perinatal history, family history of asthma, and exposure to smoking were similar in patients with and without airway obstruction. The height and weight were and remained within the normal range. We conclude that gradual normalization of air-trapping continues well into adolescence in virtually all patients with a history of prematurity and chronic lung disease. In contrast, airflow obstruction may persist but does not get worse later in life. Although chronic airflow obstruction probably is the consequence of injury to the small airways during the neonatal period, it is present in only some of the children, and it does not appear to be directly related to the perinatal history. Finally, there is evidence that airway hyperresponsiveness may be a contributing factor to the development and/or persistence of airflow obstruction in chronic lung disease of prematurity. Pediatr Pulmonol. 1996; 21:28–34 . © 1996 Wiley-Liss, Inc.     

Bronchial hyperresponsiveness in an adult population in Helsinki: decreased FEV1, the main determinant

Introduction: Bronchial hyperresponsiveness (BHR) elevates the risk for development of respiratory symptoms and accelerates the decline in forced expiratory volume in the first second (FEV₁). We thus aimed to assess the prevalence, determinants and quantity of BHR in Helsinki. Objectives: This study involved 292 randomly selected subjects age 26–66 years, women comprising 58%. Methods: Following a structured interview, a spirometry, a bronchodilation test, and a skin‐prick test, we assessed a bronchial challenge test with inhaled histamine using a dosimetric tidal breathing method. Results included the provocative dose inducing a decrease in FEV₁ by 15% (PD₁₅FEV₁) and the dose‐response slope. For statistical risk factor‐analyses, the severity of BHR was considered; PD₁₅ values ≤1.6 mg (BHR) and ≤0.4 mg [moderate or severe BHR (BHR_ms)] served as cut‐off levels. Results: BHR presented in 21.2% and BHR_ms in 6.2% of the subjects. FEV₁ < 80% of predicted [odds ratio (OR) 4.09], airway obstruction (FEV₁/forced vital capacity < 88% of predicted) (OR 4.33) and history of respiratory infection at age <5 (OR 2.65) yielded an increased risk for BHR as ORs in multivariate analysis. For BHR_ms, the determinants were decreased FEV₁ below 80% of predicted (OR 27.18) and airway obstruction (OR 6.16). Respiratory symptoms and asthma medication showed a significant association with BHR. Conclusions: Of the adult population of Helsinki, 21% showed BHR to inhaled histamine. The main determinants were decreased FEV₁ and airway obstruction. Quantitative assessment of BHR by different cut‐off levels provides a tool for characterization of phenotypes of airway disorders in epidemiologic and clinical studies. Please cite this paper as: Juusela M, Pallasaho P, Sarna S, Piirilä P, Lundbäck B and Sovijärvi A. Bronchial hyperresponsiveness in an adult population in Helsinki: decreased FEV₁, the main determinant. Clin Respir J 2013; 7: 34–44.     

Effect of Obesity on Asthma Phenotype is Dependent upon Asthma Severity

Background. We recently reported that obese and non-obese patients with asthma have similar airflow limitation and bronchodilator responsiveness, but obese patients have more symptoms overall. There is limited information on the effect of obesity on asthmatics of varying severity measured by objective physiological parameters. Understanding how obesity affects asthmatics of differing severity can provide insights into the pathogenesis of asthma in the obese and a rationale for the therapeutic approach to such patients. Methods. Participants with asthma from two American Lung Association—Asthma Clinical Research Center (ALA-ACRC) studies were grouped by tertiles of airflow obstruction (forced expiratory volume in one second (FEV₁%) predicted, FEV₁/forced vital capacity (FVC)) and methacholine reactivity (PC₂₀FEV₁). Within each tertile, we examined the independent effect of body mass index (BMI), divided into normal weight, overweight, and obese categories, on lung function, airway reactivity, and symptoms. Results. Overall, both FEV₁ and FVC decreased and symptoms worsened with increasing BMI; airway reactivity was unchanged. When stratified by the degree of airflow obstruction, higher BMI was not associated with greater airway reactivity to methacholine. Higher BMI was associated with more asthma symptoms only in the least obstructed FEV₁/FVC tertile. When stratified by degree of airway reactivity, BMI was inversely associated with FVC in all PC₂₀FEV₁ tertiles. BMI was directly associated with asthma symptoms only in those with the least airway reactivity. Conclusions. Obesity does not influence airway reactivity in patients with asthma and it is associated with more symptoms only in those with less severe disease.     

Emergency room assessment and treatment of patients with acute asthma: Adequacy of the conventional approach

The adequacy of emergency room treatment of patients with acute severe asthma was assessed by analyzing the course of 127 visits to the emergency room by 102 patients. Using conventional clinical criteria as an end point (i.e., disappearance of dyspnea, elimination of labored breathing and reduction or elimination of wheezing) in 85.4 per cent of these episodes the patients responded sufficiently to emergency room treatment to allow their discharge. However, the relief of airway obstruction measured directly (1 second forced expiratory volume, FEV₁) was modest (mean FEV₁ on discharge was 57 per cent of the predicted normal value). Approximately one-quarter of those episodes that ended in the patient's discharge from the emergency room were followed by equally severe episodes within 10 days (relapse); 6 per cent of the patients initially discharged who returned to the emergency room required hospitalization. Subjects who had a relapse had significantly less improvement in FEV₁ during treatment and lower FEV₁ values at discharge than those who did not have a relapse (p < 0.05). Finally no clinical or conventional laboratory parameter (e.g., pulsus paradoxicus, sternomastoid muscle contraction, arterial carbon dioxide [PaCO₂] or oxygen [PaO₂] tension) was sufficiently reliable as an index of the degree of obstruction to substitute for the FEV₁. We conclude that (1) the success of emergency room treatment depends on the degree of improvement in pulmonary function achieved; and (2) objective measures (e.g., FEV₁) of the degree of airway obstruction are helpful in predicting the outcome of emergency room treatment of patients with acute asthma.     

A reduction in maximum mid-expiratory flow rate. A spirographic manifestation of small airway disease

We studied the pulmonary function of fifty-three nonasthmatic patients who were heavy smokers and who complained of bouts of wheezing, cough and sputum production. The only findings on routine pulmonary function studies were a reduced maximum mid-expiratory flow rate (MMF) and an enlarged residual volume (RV). Airway resistance (Raw), specific conductance, one second forced expiratory volume (FEV₁), maximum expiratory flow rate (MEFR) and total lung capacity (TLC) were all within predicted statistical norms. In twenty-five patients we measured static (Cstat) and dynamic compliance (Cdyn) and gas exchange both at rest and during exercise. Cstat was found to be normal in every case, but Cdyn was frequency dependent. Physiologic dead space to tidal volume ratios (V_D:V_T) and alveolar-arterial gradients for oxygen (A-aDO₂) were found to be abnormally elevated both at rest and during exercise. After treatment with oral bronchodilators for one month the MMF improved in twenty-one patients. Cessation of smoking combined with the bronchodilators therapy completely reversed all the functional abnormalities in four subjects. We postulate that the low MMF represents significant airway obstruction in peripheral bronchioles and as such may represent an early manifestation of chronic bronchitis when the disease may be amenable to therapy.     

Off-Line Fractional Exhaled Nitric Oxide Measurement Is Useful to Screen Allergic Airway Inflammation in an Adult Population

To determine whether off-line fractional exhaled nitric oxide (FeNO) measurement is applicable to screen allergic airway inflammation for epidemiologic studies, we examined 280 adults, measuring off-line FeNO samplings, pulmonary function, and serum immunoglobulin E (IgE). Subjects with recurrent wheeze (recurrent wheezers) had significantly higher FeNO and IgE levels and significantly lower forced expiratory volume in 1 second/forced vital capacity (FEV₁/FVC) than non-wheezers. Statistical analysis showed that FeNO and FEV₁/FVC were significant predictors for recurrent wheezers, independent of smoking. The cut-off FeNO level for screening allergic airway inflammation was 38 ppb in non-smokers and 32.9 ppb in smokers. Thus, off-line FeNO can be used as a good marker to screen allergic airway inflammation, regardless of smoking.     

Reversible airway obstruction in rheumatic mitral valve disease

Lung function was studied in 24 patients with advanced mitral stenosis scheduled for mitral valve replacement (MVR), and revealed an obstructive ventilatory pattern [rewording of this sentence OK] . Forty per cent of the patients had a forced expiratory volume in 1 s (FEV₁)<60% of that predicted in the preoperative period. Twenty-five per cent of those operated upon showed a similar pattern up to 110 weeks postoperatively. A blind study of the effect of placebo and β₂ agonist (salbutamol) inhalation was performed preoperatively and 6 months postoperatively, to evaluate the reversibility of airflow obstruction in these patients, flow volume curve and body plethysmographic measurement of airway resistance (Rex) and intrathoracic gas volume (VTG). Patients in the pre and postoperative period showed a significant difference between the placebo and the β₂ agonist responses for FEV₁, FEV₁ as percentage of FVC (FEV₁% FVC), peak expiratory flow rate (PEFR), flow rate of 50% of expiratory vital capacity ([¨max₅₀), Rex and VTG (P<0.001). We conclude that salbutamol inhalation improves obstructive impairment in patients with MVR pre- and postoperatively.     

An Evaluation of Levalbuterol HFA in the Prevention of Exercise-Induced Bronchospasm

Background. Exercise-induced bronchospasm (EIB) affects up to 90% of all patients with asthma. Objective. This study evaluated the ability of levalbuterol hydrofluoroalkane (HFA) 90 μg (two actuations of 45 μg) administered via metered dose inhaler (MDI) to protect against EIB in mild-to-moderate asthmatics. Methods. This was a randomized, double-blind, placebo-controlled, two-way cross-over study. Patients with asthma (n = 15) were ≥18 years, had a ≥6-month history of EIB, ≥ 70% baseline predicted forced expiratory volume in 1 second (FEV₁), and a 20% to 50% decrease in FEV₁ after treadmill exercise challenge using single-blind placebo MDI. Levalbuterol or placebo was self-administered 30 minutes before exercise. Treatment sequences were separated by a 3-to 7-day washout period. Spirometry was performed predose, 20 minutes postdose/pre-exercise, and 5, 10, 15, 30, and 60 minutes post-exercise. The primary endpoint was the maximum percent decrease in FEV₁ from baseline (postdose/pre-exercise). The percentage of protected (≤ 20% decrease in post-exercise FEV₁) patients was also assessed. Results. Levalbuterol had significantly smaller maximum percent post-exercise decrease in FEV₁ compared with placebo (LS mean ± SE; ?4.8% ± 2.8% versus ?22.5% ± 2.8%, respectively). For levalbuterol, 14/15 (93.3%) patients had < 20% decrease in post-exercise FEV₁ compared with 8/15 (53.3%) for placebo (p = 0.0143). Treatment was well tolerated. Conclusion. Levalbuterol HFA MDI (90 μg) administered 30 minutes before exercise was significantly more effective than placebo in protecting against EIB after a single exercise challenge and was well tolerated. Clinical Implications. Levalbuterol HFA MDI when administered before exercise was effective in protecting adults with asthma from EIB.     

Spirometric patterns in childhood asthma: Peak flow compared with other indices

The objective of this study was to determine patterns of pulmonary function abnormalities and to evaluate how adequately peak flow monitoring was correlated to other spirometric indices in childhood asthma. Ninety-one children, aged 8-15 years, with moderate-to-severe asthma were repeatedly tested in a summer camp. On-site medical staff permitted 24-hour-a-day supervision. Subjective and objective clinical evaluations of asthma status were made over 14 consecutive days. Detailed clinical history and clinical observations were made by an experienced staff, and a total of 2,663 pulmonary function tests were performed regularly three times daily and whenever a child sensed asthma symptoms. Patterns of obstruction were divided into large airway abnormalities and small airway abnormalities. There was a low concordance between standard large airway measures, such as the peak expiratory flow rate (PEFR) or the forced expiratory volume in 1 second (the FEV₁), and measures of small airway obstruction, such as the forced expiratory flow rate 25-75% (FEF_25–75). Normal PEFR measurements do not always indicate that all other pulmonary function measures are normal. In fact, 18% of children with a normal PEFR had abnormal FEF_25–75 values. Results demonstrated that the FEF_25–75 was the most specific and sensitive measure of airway obstruction. PEFR is widely used to monitor asthma symptoms objectively because it is technically simple to perform, relatively inexpensive, and helpful in most cases. It is, therefore, appropriate for asthma education programs to recommend PEFR as an objective measure to guide in making therapeutic decisions. Our data and clinical observations support the “Guidelines for the Diagnosis and Management of Asthma” of the NIH Health Asthma Education Program that suggest that children have more complete pulmonary function testing along with frequent PEFR measures. Many children may appear asymptomatic, while recording normal PEFR measures, and still having significant asthma. Repeated pulmonary function testing and evaluation of the pattern of respiratory obstruction aids in managing this challenging group. We recommend that efforts be made to develop a simple and inexpensive method of measuring FEF_25–75 that will allow this measurement to be made even at home. Pediatr Pulmonol. 1995; 20:372–379 . © 1995 Wiley-Liss, Inc.