Serial Measurements Of Lung Function Research Articles

Differences and agreement between two portable hand-held spirometers across diverse community-based populations in the Prospective Urban Rural Epidemiology (PURE) study.

Portable spirometers are commonly used in longitudinal epidemiological studies to measure and track the forced expiratory volume in first second (FEV1) and forced vital capacity (FVC). During the course of the study, it may be necessary to replace spirometers with a different model. This raise questions regarding the comparability of measurements from different devices. We examined the correlation, mean differences and agreement between two different spirometers, across diverse populations and different participant characteristics. From June 2015 to Jan 2018, a total of 4,603 adults were enrolled from 628 communities in 18 countries and 7 regions of the world. Each participant performed concurrent measurements from the MicroGP and EasyOne spirometer. Measurements were compared by the intra-class correlation coefficient (ICC) and Bland-Altman method. Approximately 65% of the participants achieved clinically acceptable quality measurements. Overall correlations between paired FEV1 (ICC 0.88 [95% CI 0.87, 0.88]) and FVC (ICC 0.84 [0.83, 0.85]) were high. Mean differences between paired FEV1 (-0.038 L [-0.053, -0.023]) and FVC (0.033 L [0.012, 0.054]) were small. The 95% limits of agreement were wide but unbiased (FEV1 984, -1060; FVC 1460, -1394). Similar findings were observed across regions. The source of variation between spirometers was mainly at the participant level. Older age, higher body mass index, tobacco smoking and known COPD/asthma did not adversely impact on the inter-device variability. Furthermore, there were small and acceptable mean differences between paired FEV1 and FVC z-scores using the Global Lung Initiative normative values, suggesting minimal impact on lung function interpretation. In this multicenter, diverse community-based cohort study, measurements from two portable spirometers provided good correlation, small and unbiased differences between measurements. These data support their interchangeable use across diverse populations to provide accurate trends in serial lung function measurements in epidemiological studies.

Ethnicity, socioeconomic status and the severity and course of non-cystic fibrosis bronchiectasis.

This study evaluated whether there are ethnic factors which affect the severity and progression of bronchiectasis in our adult multi-ethnic population in Auckland, New Zealand. Clinical records were reviewed from patients attending the outpatient facilities of our institution between 2007 and 2010. Data collected included demographics, clinical features, smoking status, self-reported ethnicity, socioeconomic status (NZDep), pulmonary function and sputum microbiology. A total of 437 patients was identified: median age 65 years, 66% female, mean forced expiratory volume in the first second (FEV1 ) 62.4% predicted, and 10.5% of patients had recurrent growth of Pseudomonas aeruginosa. Patients of Maori and Pacific ethnicity were overrepresented compared to the institution population catchment and had more severe impairment of lung function: mean % predicted FEV1 for Pacific 52.0, Maori 58.6, European 68.6, Asian 64.2 (P < 0.0001). This was independent of socioeconomic status. However, no overall decline was seen in serial lung function measurements, either across the whole cohort or in any particular ethnic group. Patients of Maori and Pacific ethnicity are both overrepresented and have more severe bronchiectasis in this cohort, independent of socioeconomic status. Ethnicity did not predict decline in pulmonary function. Further studies into genetic predisposition to bronchiectasis in Maori or Pacific people may be warranted.

Spirometer Replacement and Serial Lung Function Measurements in Population Studies: Results From the SAPALDIA Study.

The Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA), a population cohort study, used heated-wire spirometers in 1991 and 2002 and then ultrasonic spirometers in 2010 revealing measurement bias in healthy never smokers. To provide a practical method to control for measurement bias given the replacement of spirometer in long-term population studies, we built spirometer-specific reference equations from healthy never smokers participating in 1991, 2002, and 2010 to derive individualized corrections terms. We compared yearly lung function decline without corrections terms with fixed terms that were obtained from a quasi-experimental study and individualized terms. Compared with baseline reference equations, spirometer-specific reference equations predicted lower lung function. The mean measurement bias increased with age and height. The decline in forced expiratory volume in 1 second during the reference period of 1991-2002 was 31.5 (standard deviation (SD), 28.7) mL/year while, after spirometer replacement, uncorrected, corrected by fixed term, and individualized term, the declines were 47.0 (SD, 30.1), 40.4 (SD, 30.1), and 30.4 (SD, 29.9) mL/year, respectively. In healthy never smokers, ultrasonic spirometers record lower lung function values than heated-wire spirometers. This measurement bias is sizeable enough to be relevant for researchers and clinicians. Future reference equations should account for not only anthropometric variables but also spirometer type. We provide a novel method to address spirometer replacement in cohort studies.

Postinfectious bronchiolitis obliterans in children: lessons from bronchiolitis obliterans after lung transplantation and hematopoietic stem cell transplantation

Postinfectious bronchiolitis obliterans (PIBO) is an irreversible obstructive lung disease characterized by subepithelial inflammation and fibrotic narrowing of the bronchioles after lower respiratory tract infection during childhood, especially early childhood. Although diagnosis of PIBO should be confirmed by histopathology, it is generally based on history and clinical findings. Irreversible airway obstruction is demonstrated by decreased forced expiratory volume in 1 second with an absent bronchodilator response, and by mosaic perfusion, air trapping, and/or bronchiectasis on computed tomography images. However, lung function tests using spirometry are not feasible in young children, and most cases of PIBO develop during early childhood. Further studies focused on obtaining serial measurements of lung function in infants and toddlers with a risk of bronchiolitis obliterans (BO) after lower respiratory tract infection are therefore needed. Although an optimal treatment for PIBO has not been established, corticosteroids have been used to target the inflammatory component. Other treatment modalities for BO after lung transplantation or hematopoietic stem cell transplantation have been studied in clinical trials, and the results can be extrapolated for the treatment of PIBO. Lung transplantation remains the final option for children with PIBO who have progressed to end-stage lung disease.

Serial measurements of exhaled nitric oxide at work and at home: a new tool for the diagnosis of occupational asthma.

Whereas serial measurements of lung function at work and at home are a well-known diagnostic tool for the diagnosis of occupational asthma (OA), little is known about the serial measurements of non-invasive parameters such as exhaled nitric oxide (eNO). A 51-year-old baker with variable shortness of breath without relation to work was examined for suspected OA. Skin prick test showed weak sensitizations to wheat and rye flour (without sensitizations to environmental allergens) that were corroborated by in vitro testing (CAP class 3). Baseline FEV1 of 58% predicted and a decrease of forced expiratory volume in 1 s (FEV1) after placebo (sugar powder) of 17% did not allow inhalational challenge testing. The patient performed daily measurements of FEV1 and eNO for about a month during a holiday at home and at work. Whereas symptoms and FEV1 did not show differences between holidays and work periods, eNO showed a clear increase from below 10 ppb to a maximum of 75 ppb. A diagnosis of baker's asthma was made, and the patient quit his job immediately after medical advice. A year afterwards, the patient was still taking asthma medication, but his symptoms had improved, FEV1 had increased to 73% predicted, and eNO was 25 ppb. We conclude that serial measurements of eNO at home and at work may be a useful tool for the diagnosis of OA.

Management of status asthmaticus in children

Recent literature on paediatric status asthmaticus (PSA) confirms an increasing percentage of admissions to paediatric intensive care units. PSA is a medical emergency that can be fatal and needs careful and prompt intervention. The severity of PSA is mainly determined by clinical judgement of signs and symptoms. Peak flow measurements and serial lung function measurements are not reliable in PSA. Validated clinically useful instruments are lacking. The three main factors that are involved in the pathophysiology of PSA, bronchoconstriction, mucus plugging and airway inflammation need to be addressed to optimise treatment. Initial therapies include supplementation of oxygen, repetitive administration of rapid acting β2-agonists, inhaled anticholinergics in combination with systemic glucocorticosteroids and intravenous magnesium sulphate. Additional treatment modalities may include methylxanthines, DNase, ketamine, sodium bicarbonate, heliox, epinephrine, non-invasive respiratory support, mechanical ventilation and inhalational anaesthetics.

Long-term nose-only cigarette smoke exposure induces emphysema and mild skeletal muscle dysfunction in mice

SUMMARYMouse models of chronic obstructive pulmonary disease (COPD) focus on airway inflammation and lung histology, but their use has been hampered by the lack of pulmonary function data in their assessment. Systemic effects such as muscle dysfunction are also poorly modeled in emphysematous mice. We aimed to develop a cigarette-smoke-induced emphysema mouse model in which serial lung function and muscular dysfunction could be assessed, allowing the disease to be monitored more appropriately. C57Bl6 mice were nose-only exposed to cigarette smoke or filtered air for 3–6 months. Lung function tests were repeated in the same mice after 3 and 6 months of cigarette smoke or air exposure and compared with lung histological changes. Contractile properties of skeletal muscles and muscle histology were also determined at similar time points in separate groups of mice. Serial lung function measurements documented hyperinflation after 3 and 6 months of cigarette smoke exposure, with a significant 31–37% increase in total lung capacity (TLC) and a significant 26–35% increase in compliance (Cchord) when compared with animals exposed to filtered air only (P<0.001 after 3 and after 6 months). These functional changes preceded the changes in mean linear intercept, which became only significant after 6 months of cigarette smoke exposure and which correlated very well with TLC (r=0.74, P=0.004) and Cchord (r=0.79, P=0.001). After 6 months of cigarette smoke exposure, a significant fiber-type shift from IIa to IIx/b was also observed in the soleus muscle (P<0.05), whereas a 20% reduction of force was present at high stimulation frequencies (80 Hz; P=0.09). The extensor digitorum longus (EDL) muscle was not affected by cigarette smoke exposure. These serial pulmonary function variables are sensitive outcomes to detect emphysema progression in a nose-only cigarette-smoke-exposed animal model of COPD. In this model, muscular changes became apparent only after 6 months, particularly in muscles with a mixed fiber-type composition.

Fcγ receptor IIIb (CD16b) polymorphisms are associated with susceptibility to idiopathic pulmonary fibrosis.

An excess of neutrophils in the alveoli and lung interstitium has been described in idiopathic pulmonary fibrosis (IPF). Engagement of neutrophil Fcγ receptors with IgG complexes may contribute to the pathogenesis of IPF. The neutrophil FcγRIIIb receptor occurs in two codominantly expressed allelic variants, NA1 and NA2, which exhibit different binding affinities for IgG1 and IgG3 subclasses. The aim of this study was to investigate whether FcγRIIIb genotype is associated with IPF susceptibility or disease progression. In a case-control study we compared the distribution of FcγRIIIb NA1/2 polymorphisms in 142 patients with IPF and in 218 controls using allele-specific PCR amplification. Significant skewing in the distribution of FcγRIIIb genotypes was observed between patients with IPF and control subjects. In the IPF cohort, there was higher frequency of the NA1/NA1 genotype (0.19 vs. 0.07), and lower NA2/NA2 frequency (0.31 vs. 0.50; χ(2) = 17.71, df = 2, P < 0.001). The overall frequency of the NA1 allele was increased in IPF patients compared to controls (0.44 vs. 0.29; P < 0.0001, odds ratio [OR] = 1.93, 95% confidence interval [CI] = 1.42-2.64). Heterozygotes and homozygotes of the NA1 allele were at higher risk of developing IPF (OR = 2.19, 95% CI = 1.40-3.41, P = 0.0005), whereas the NA2 allele was protective against IPF (OR = 0.34, 95% CI = 0.17-0.65, P = 0.0014). There was no association of FcγRIIIb genotype with disease progression as assessed by serial lung function measurements. FcγRIIIb NA1/2 polymorphisms are associated with IPF disease susceptibility. These results support a role for immunological mechanisms contributing to IPF pathogenesis.

Serial Measurements of Lung Function in a Cohort of Young Children With Bronchopulmonary Dysplasia

We aimed to prospectively and longitudinally measure lung function in a cohort of children with bronchopulmonary dysplasia (BPD) during their first 3 years of life. Forty-four children with BPD with a mean (+ or - SD) gestational age of 25.6 (+ or - 1.7) weeks and birth weight of 0.767 (+ or - 0.2) kg underwent serial measurements of lung function (maximum flow at functional residual capacity [V(max)FRC] and functional residual capacity [FRC]) at 6, 12, and 24 months after initial discharge from the neonatal care unit. Compared with normative data, children with BPD had low partial expiratory airflow, measured by V(max)FRC, with mean z score (+ or - SD) of -1.92 (+ or - 1.04), -1.79 (+ or - 1.5), and -1.67 (+ or - 1.5) at 6, 12, and 24 months, respectively. Over time there was no significant improvement in z scores (P = .66), and 45% of the patients had a z score value of less than -2 (2 SDs below the mean) at the end of the study. FRC measurements steadily and significantly increased over time. Partial expiratory flow showed no correlation with gestational age, birth weight, or length of mechanical ventilation. Mean FRC was significantly higher in children who were using bronchodilators and inhaled steroids but showed no correlation with clinical symptoms. Bronchodilator response was initially present in 30% of the patients and declined to 20% at the end of the study. During the first 3 years of life, children with mostly moderate-to-severe BPD continue to show significant abnormalities with airflow limitation according to lung-function testing.

Protective effect of budesonide/formoterol compared with formoterol, salbutamol and placebo on repeated provocations with inhaled AMP in patients with asthma: a randomised, double-blind, cross-over study

BackgroundThe budesonide/formoterol combination is successfully used for fast relief of asthma symptoms in addition to its use as maintenance therapy. The temporarily increased corticosteroid dose during increasing inhaler use for symptom relief is likely to suppress any temporary increase in airway inflammation and may mitigate or prevent asthma exacerbations. The relative contribution of the budesonide and formoterol components to the improved asthma control is unclear.MethodsThe acute protective effect of inhaled budesonide was tested in a model of temporarily increased airway inflammation with repeated indirect airway challenges, mimicking an acute asthma exacerbation. A randomised, double-blind, cross-over study design was used. Asthmatic patients (n = 17, mean FEV1 95% of predicted) who previously demonstrated a ≥30% fall in forced expiratory volume in 1 second (FEV1) after inhaling adenosine 5'-monophosphate (AMP), were challenged on four consecutive test days, with the same dose of AMP (at 09:00, 12:00 and 16:00 hours). Within 1 minute of the maximal AMP-induced bronchoconstriction at 09:00 hours, the patients inhaled one dose of either budesonide/formoterol (160/4.5 μg), formoterol (4.5 μg), salbutamol (2 × 100 μg) or placebo. The protective effects of the randomised treatments were assessed by serial lung function measurements over the test day.ResultsIn the AMP provocations at 3 and 7 hours after inhalation, the budesonide/formoterol combination provided a greater protective effect against AMP-induced bronchoconstriction compared with formoterol alone, salbutamol and placebo. In addition all three active treatments significantly increased FEV1 within 3 minutes of administration, at a time when inhaled AMP had induced the 30% fall in FEV1.ConclusionsA single dose of budesonide/formoterol provided a greater protective effect against inhaled AMP-induced bronchoconstriction than formoterol alone, both at 3 and at 7 hours after inhalation. The acute protection against subsequent bronchoconstrictor stimuli such as inhaled AMP and the rapid reversal of airway obstruction supports the use of budesonide/formoterol for both relief and prevention in the treatment of asthma.Trial RegistrationClinicalTrials.gov number NCT00272753

Predicting response to therapy in acute asthma

To analyze the prediction of response of therapy into the context of acute adult asthma assessment in the emergency department (ED) setting. Close monitoring of the patient's condition at presentation (static assessment) and response to treatment (dynamic assessment), including serial measurements of lung function, is an essential part of the acute asthma care in the ED. The severity of airflow obstruction cannot be accurately judged by patient's symptoms and physical examination alone. Accordingly, it is very important to use an objective measure of airway obstruction (spirometry or peak flow meter). Although spirometry can be performed in acutely ill ED asthmatics, measurement of peak expiratory flow, with values expressed as predicted normal values, represents an alternative if spirometry is not available. Failure of initial therapy to improve expiratory flow predicts a more severe course and need for hospitalization. Although several score systems have been developed, different factors limit their applicability in the ED setting. Thus, peak expiratory flow rate measures at 15-60 min of treatment, joined with continuous monitoring of oxygen saturation may be the best ways to assess patients with acute asthma.

Ventilation Inhomogeneities in Relation to Standard Lung Function in Patients with Cystic Fibrosis

Based on serial lung function measurements performed in 142 children (68 males; 74 females) with cystic fibrosis (CF), prospectively evaluated over an age range of 6 to 20 years, we attempted to determine whether the lung clearance index (LCI) as a measure of ventilation inhomogeneities could be a discriminating factor of disease progression. Annual follow-up lung function measurements featuring FRC determined by whole-body plethysmography and multibreath nitrogen washouts, effective specific airway resistance, flow-volume curves, LCI, and gas exchange characteristics were analyzed by linear mixed-model analysis and Kaplan-Meier statistics. The earliest occurring and strongest factor of progression was the LCI, followed by maximal expiratory flow (MEF(50)) and FRC determined by plethysmography (p < 0.0001). Associations between onset of chronic Pseudomonas aeruginosa infection and CF transmembrane conductance regulator (CFTR) genotype with FEV(1) (p = 0.027) and FVC (p = 0.007) were identified. The study shows that the LCI predicts earlier in life and represented much better functional progression than FEV(1). Moreover, there is no single functional predictor of progression in CF, but aside from risk factors, such as onset of chronic P. aeruginosa infection and genotype, pulmonary hyperinflation, airway obstruction, and ventilation inhomogeneities are important pathophysiologic processes that should be evaluated concomitantly as determinants of lung progression in CF.

Improved activities of daily living, psychological state and health-related quality of life for 12 months following lung volume reduction surgery in patients with severe emphysema.

The aim of the present study was to evaluate the effect of lung volume reduction surgery (LVRS), with an emphasis on improvement in activities of daily living (ADL), psychological state and health-related quality of life (HRQL), for 12 months in patients with severe emphysema. Eighteen male patients (mean age +/- SD: 65.2 +/- 6.4 years) who underwent LVRS following pulmonary rehabilitation (LVRS group) and 12 patients (67.0 +/- 8.1 years) who were medicated and underwent pulmonary rehabilitation (non-LVRS group) were studied. LVRS was performed by video-assisted thoracoscopic surgery. Serial measurements of lung function, 6-min walking distance (6MWD), ADL, HRQL and psychological state scores were performed before surgery and 3, 6, and 12 months after surgery (in the LVRS group), or on the day of discharge (in the non-LVRS group). As well as an improvement in FEV(1) and 6MWD, ADL scores were significantly improved in the items of 'face washing and teeth brushing', and 'indoor walking' at 3 months after LVRS (P < 0.05). At 12 months, an improvement was still found in 'indoor walking' and 'bathing'. HRQL scores were ameliorated at 3-12 months after LVRS. In the non-LVRS group, ADL and HRQL scores failed to improve in any items during the 12 months of observation. Psychological state scores were maintained in the LVRS group and were better than those in the non-LVRS group at 12 months (P < 0.05). Lung volume reduction surgery improves not only lung function and exercise performance but also ADL, HRQL and psychological state for at least 12 months.

Management of asthma exacerbations

The 1997 Expert Panel Report 2 from the National Asthma Education and Prevention Program details principles and goals for managing asthma exacerbations, based on scientific literature and the opinion of the panel. The panel's recommendations are summarized here, along with approaches to the evaluation and management of patients with asthma exacerbations. Methods to assess and classify the severity of asthma exacerbations are discussed, and treatment objectives for mild, moderate, and severe exacerbations are presented, along with a discussion of postinfectious acute airway hyperresponsiveness. A review of pharmacologic agents used in the treatment of asthma exacerbations is also included. Key points in the management of asthma exacerbations include the notion that early treatment is the best strategy for management. Important elements of early treatment include recognition of early signs of worsening asthma, a written action plan to guide patient self-management, appropriate intensification of therapy, and prompt communication between patient and provider about deterioration in asthma control. Other key points include the use of inhaled β 2-adrenergic agonists to provide prompt relief of airflow obstruction, the early use of systemic corticosteroids for patients with moderate to severe exacerbations or for patients who fail to respond promptly and completely to an inhaled f2-adrenergic agonist, and monitoring response to therapy with serial measurements of lung function.

Using Statistical Process Control Charts for the Continual Improvement of Asthma Care

Home monitoring of lung function using simple, inexpensive tools to measure peak expiratory flow rate (PEFR) has been possible since the 1970s. Yet although current national and international guidelines recommend monitoring of PEFRs via traditional run charts, their use by both patients and physicians remains low. The role of statistical process control (SPC) theory and charts in the serial monitoring of lung function at home were explored and applied to the direct care of patients with asthma. The method represents an integration of collective professional and improvement knowledge with the related disciplines of continual improvement, SPC, system thinking/system dynamics, paradigms, and the learning community/organization. Use of PEFR control charts for four patients cared for at the Asthma-Allergy Clinic and Research Center (Shreveport, La) is described. The key to good asthma control is the ability to optimize lung function by reducing the variation between serial lung function measurements and thereby generate a safe range of function. Knowledge of the type of variation (special cause or common cause) in the system helps in focusing clinical decision making. Case 4, an 11-year-old boy, for example, shows how control charts were used to learn the effects of a new inhaled corticosteroid. Comparison of the last 14 days of baseline and the last 14 days of open label use of the inhaled corticosteroid showed an obvious improvement in actual PEFR values--which a run chart or comparison of means would have easily demonstrated. The control chart showed that this child's care process at baseline was functionally at risk for severe asthma (46% personal best) and that the effect of the new medication not only elevated the mean function but shifted the range of function from 46%-72% personal best to 78%-102% personal best. At this new range of function the patient's system of care was not capable of delivering values that are at risk for severe asthma. Unless the range of function the change in care is capable of producing is specifically quantitated, misinterpretation of improvement data can occur. Developing the concept of the PEFR control chart involved examining and challenging traditional mental models for monitoring PEFR at home in the care of asthma, acquiring a better understanding of the workings of dynamic systems and with system thinking, and sharing what was learned with patients and seeking their input. The PEFR control chart employs an interesting statistical platform that enables the integration of knowledge of serial measurements and knowledge of the variation between those measurements into a tool with which to better assess the asthma care process being followed. This tool provides clinical insights, practical knowledge, and opportunities unavailable to patients and physicians via traditional PEFR charting.

Management of asthma exacerbations

The 1997 Expert Panel Report 2 from the National Asthma Education and Prevention Program details principles and goals for managing asthma exacerbations, based on scientific literature and the opinion of the panel. The panel's recommendations are summarized here, along with approaches to the evaluation and management of patients with asthma exacerbations. Methods to assess and classify the severity of asthma exacerbations are discussed, and treatment objectives for mild, moderate, and severe exacerbations are presented, along with a discussion of postinfectious acute airway hyperresponsiveness. A review of pharmacologic agents used in the treatment of asthma exacerbations is also included. Key points in the management of asthma exacerbations include the notion that early treatment is the best strategy for management. Important elements of early treatment include recognition of early signs of worsening asthma, a written action plan to guide patient self-management, appropriate intensification of therapy, and prompt communication between patient and provider about deterioration in asthma control. Other key points include the use of inhaled beta 2-adrenergic agonists to provide prompt relief of airflow obstruction, the early use of systemic corticosteroids for patients with moderate to severe exacerbations or for patients who fail to respond promptly and completely to an inhaled beta 2-adrenergic agonist, and monitoring response to therapy with serial measurements of lung function.

Pulmonary function in children with homozygous alpha1-protease inhibitor deficiency.

Alpha1-protease inhibitor (alpha1-PI) deficiency is a well-recognized cause of emphysema in adults; however, the natural history of this disorder in children is unclear. Because of the paucity of data in the paediatric age group, we performed whole body plethysmography, spirometry, and diffusing capacity, in a cohort of 17 homozygous (PiZZ phenotype) children (9 females, 8 males; mean age +/- SEM 13.4 +/- 0.9, range 7-18 years) and in 17 normal schoolchildren (13.5 +/- 0.9, 7-18 years), using a matched-pair design. Blood was drawn for determination of serum alpha1-PI levels, PI phenotype, and standard biochemical tests of liver function. Among the PiZZ subjects, 12 were detected during diagnostic workup of prolonged neonatal icterus, and 5 by routine testing in paediatric patients. None had chronic respiratory symptoms except for an 18-year-old PiZZ girl with a history of recent onset of exertional dyspnoea. All were non-smokers. The Wilcoxon test was used for statistical analysis. As expected, serum alpha1-PI levels were lower in the PiZZ group (16% of the control value). A few patients had slight elevations of their liver enzymes. As for the pulmonary function parameters, differences between groups were not significant. Individual data showed no consistent abnormality in lung function except for signs of mild expiratory obstructive airway disease with hyperinflation (elevated TGV/TLC ratio) in the only symptomatic 18-year-old subject (0.63, control subject 0.49). This was unresponsive to bronchodilators. For her, augmentation therapy with intravenous infusion of alpha1-PI may be considered. Our study confirms the absence of pulmonary function abnormalities in the vast majority of children with homozygous alpha1-PI deficiency. Serial measurements of lung function may help to distinguish those individuals who require treatment with alpha1-PI from those who do not.

Serial pulmonary function tests in the diagnosis of P. carinii pneumonia

The predictive value of serial versus isolated measurements of transfer factor for carbon monoxide (TLCO) in the diagnosis of pneumocystis carinii pneumonia (PCP) in a cohort of 474 HIV-1 seropositive patients, with all stages of HIV disease, was evaluated. Two groups of patients were studied, one group with serial lung function measurements (Group 1) and another with only a single set of measurements (Group 2). During the study period 118 patients performing serial tests developed a respiratory illness of which 58 were performing monthly and 60 three monthly measurements of lung function (Group 1). In 36 patients from Group 1, where PCP was diagnosed, monthly lung function tests showed a decrease in TLCO from 68% (+/- 3.2) (SEM), (8 weeks prior to illness), to 44% (+/- 2.5) predicted normal at presentation, whereas in 22 patients who did not have PCP, TLCO fell from 71% (+/- 4.5) to 57% (+/- 3.1). TLCO was thus reduced to lower values in these with PCP than in those without PCP (p < 0.05). A fall of TLCO of 5% from initial values when used as predictive for presence of PCP had a sensitivity of 75% and a specificty of 28% (positive predictive value 56%; negative predictive value 48%). TLCO was < 70% predicted in 72/78 patients with PCP who performed only single lung function tests (Group 2), which gave a sensitivity of 92% and a specificity of 71% as a diagnostic test for PCP when compared with the cohort as a whole. The positive predictive value was 34%, negative predictive value was 98%.(ABSTRACT TRUNCATED AT 250 WORDS)

Markers for eosinophils and T-lymphocytes as predictors of late asthmatic response.

Bronchial allergen challenge was performed on 12 allergic asthmatics during a stable phase of their disease. After resolution of the immediate bronchial response, fractional lung lavage was performed twice, two and 24 h post-challenge. The recovery of eosinophils, eosinophil cationic protein (ECP), eosinophil chemotactic activity (ECA) and immunohistochemical staining of the phenotypically distinct population stainable by the monoclonal antibody CD45RO, agreed to indicate T-memory cells, were assessed in the two lavages. Serial measurements of lung function, and serum concentration of ECP were also done. We found that although the recoveries in bronchial washes of eosinophil cells and ECP tended to increase during the trial, none of these variables predicted the emergence of late phase bronchial response (LPR). Instead, the proportion in the 2-h lavages, of memory-cells or ECA predicted the LPR. These two variables were inversely correlated to each other in the first lavage, suggesting the T-cells to be potential major sources of ECA. The fact that T-cells and ECA, but not markers for eosinophil activation in lavage, predicted the LPR, may suggest T-cell activation to precede the activation of the eosinophils within the lung after a bronchial allergen challenge. There was a close correlation between LPR and serum concentration of ECP obtained at the end of the trial, 24 h post-challenge, suggesting either a delayed or a continuous activation of circulating eosinophils after bronchial allergen challenge.

Bronchial hyperresponsiveness and level of exposure in occupational asthma due to western red cedar (Thuja plicata). Serial observations before and after development of symptoms.

Four workers from a cedar sawmill who developed red cedar asthma are described. They had serial measurements of lung function and nonspecific bronchial hyperresponsiveness (NSBH) several years before and after the development of chest symptoms. Measurements of dust concentration and specific IgE antibodies to plicatic acid-human serum albumin (PA-HSA) conjugate were also carried out before the onset of disease. NSBH developed in parallel with the development of asthma and was not present in any of the workers beforehand, indicating that it is not a predisposing host factor. Nasal symptoms preceded chest symptoms in three workers, suggesting that this may be an early marker of the disease. Although dust concentrations for jobs located both inside and outside the sawmill were low, jobs associated with somewhat higher exposures were associated with the initiation of asthma symptoms.