Airflow Limitation In Patients Research Articles

The Scoring of Respiratory Events in Sleep: Reliability and Validity

The American Academy of Sleep Medicine Task Force on Respiratory Scoring reviewed the evidence that addresses: the validity of specific sensors in detecting airflow, tidal volume, oxyhemoglobin saturation, and CO2; the reliability of specific scoring approaches for quantifying sleep related breathing disorders (SRBD); and the validity of using various definitions of the apnea hypopnea index (AHI) as assessed by the strength and consistency of associations with several comorbidities (hypertension, cardiovascular disease, sleepiness, impaired quality of life, and accidents). The evidence was based on a literature search of relevant articles published through December 2004, which resulted in identifying and extracting data from 182 articles, which were graded using standardized approaches. Diverse physiological sensors have been utilized to quantify airflow limitation in patients with suspected SRBD. Although thermistry appears appropriate for identifying apneas, the available evidence did not indicate it provides valid quantification of airflow reduction. The emerging evidence evaluating the accuracy of signal detection against the gold standard measurements (e.g., pneumotachography) suggested the superiority of inductance plethysmography and nasal pressure transducers for detection of hypopneas, with some evidence that recordings from a nasal pressure transducer may better approximate flow/volume than uncalibrated inductance plethysmography. However, since the nasal pressure transducer has only recently been incorporated into large-scale studies, there are as of yet few data that address the predictive value of transducer-identified events relative to clinical or physiological outcomes. Very few studies directly compared the validity of alternative approaches for defining the duration, amplitude change, and use of corroborative data from desaturation or arousal for defining hypopneas. Many observational studies utilizing various designs and approaches for event detection have shown significant associations between measures of SRBD and health outcomes. Data from the 2 largest sleep cohort studies, the Sleep Heart Health Study and the Wisconsin Sleep Cohort, both used definitions of hypopneas based on "discernible" reductions of inductance plethysmography signals with associated desaturation and showed that the derived AHIs using these hypopnea definitions correlated with various indices of morbidity. However, it is not clear whether alternative definitions would provide comparable if not better prediction, or whether optimal approaches for event identification would vary for different outcomes. Despite these limitations, forming a consensus on optimal approaches for recording and measuring respiratory events is an important step toward generating data from different clinical or research laboratories that can be compared. However, additional research is needed, including direct comparisons of alternative measuring approaches for predicting clinical outcomes, with a need to address these issues in large samples across the age spectrum and with inclusion of promising new technology.

Clinical and Radiographic Indices Associated With Airflow Limitation in Patients With Sarcoidosis

Airflow limitation is found in some patients with sarcoidosis, and it is associated with a poor prognosis. The aim of this study was to investigate clinical and radiographic indices associated with airflow limitation in patients with sarcoidosis. A prospective, observational study was performed on 228 consecutive sarcoidosis patients followed up at our patient clinic at the Central Clinic of Kyoto. Patients underwent pulmonary function tests, and high-resolution CT (HRCT) of the lung was evaluated for the presence of lymph node enlargement, lung opacity, reticular shadow, and thickening of bronchovascular bundles (BVB). Airflow limitation was defined as FEV(1)/FVC < 70%. Airway reversibility was tested in subjects with airflow limitation. The frequency of airflow limitation was evaluated, and clinical and radiographic parameters were compared between patients with and without airflow limitation. Among all 228 subjects, 20 subjects (8.8%) had airflow limitation, and none showed airway reversibility. Patients with airflow limitation were predominantly male, smokers, and had advanced chest radiographic stage, increased frequency of lung opacities, reticular shadows, and thickened BVB on HRCT. Stepwise regression analysis showed that chest radiographic stage IV, higher age, smoking, and thickened BVB were independently associated with lower FEV(1)/FVC. The frequency of airflow limitation was 8.8% in Japanese sarcoidosis patients. Chest radiographic stage IV, higher age, smoking, and thickened BVB were associated with airflow limitation in patients with sarcoidosis.

Deficient alpha-1-antitrypsin phenotypes and persistent airflow limitation in severe asthma

Persistent airflow limitation is common among patients with severe asthma, but its pathogenesis has not been fully clarified. Severe alpha-1-antitrypsin (AAT) deficiency is a risk factor of chronic airflow limitation and emphysema, and partially deficient phenotypes have been associated with an accelerated decline in lung function. We hypothesized that partial deficiency of AAT (non-PiM AAT phenotype) is a risk factor of persistent airflow limitation in asthma. In 122 patients with severe asthma (86 females; age (median (range)): 44.0 yr (18-75)) postbronchodilator FEV1 and FEV1/VC were measured and the AAT phenotype was determined. Persistent airflow limitation was defined as postbronchodilator FEV1 or FEV1/VC < 75% pred. with TLC > 75% pred. Six patients (4.9%) had a non-PiM phenotype (1 MF, 3 MS, 1 MZ and 1 SZ). Of the 58 patients with persistent airflow limitation only 1 patient (1.7%) had a non-PiM phenotype vs. 7.8% among the patients without persistent airflow limitation (P = 0.21). Postbronchodilator FEV1/VC (% pred.) was higher in the non-PiM patients than in the PiM patients (P = 0.02), the other lung function parameters were not different. Linear regression analysis showed no association between AAT phenotype and FEV1% predicted (P = 0.26). AAT heterozygoty does not seem to be an important risk factor of persistent airflow limitation in patients with asthma. Although confirmation by longitudinal follow-up studies with larger sample sizes is needed, these results suggest that routine assessment of the AAT phenotype is not indicated in asthmatic patients even if they exhibit fixed airflow limitation.

Determinants of Bronchodilator Responsiveness in Patients with Controlled Asthma

Short-term bronchodilator responsiveness to an inhaled β 2 adrenergic agonist was assessed by changes in forced expiratory volume in 1 second (FEV1) in nonsmoking adults with controlled asthma (mild disease, 20 patients; moderate disease, 20 patients; severe disease, 18 patients). Responsiveness correlated significantly with age and with percent of predicted FEV1 (%FEV1) except in patients with severe asthma, who showed significantly less responsiveness than others. Thus, responsiveness is closely associated with degree of airflow limitation in patients with controlled asthma and is significantly influenced by severity of disease and by aging.

Prevalence of Previously Undiagnosed Airflow Limitation in Patients Who Underwent Preoperative Pulmonary Function Test

Although being a rapidly expanding socioeconomical burden worldwide, chronic obstructive pulmonary disease (COPD) is often overlooked because of its insidious progression. Since spirometry is the primary tool for the diagnosis of COPD, physicians should be aware of the disease in any situation where interpreting spirometry. This study was to estimate the prevalence of undiagnosed COPD among patients who underwent spirometry as a preoperative evaluation for elective surgeries. Patients aged 40 years or older who completed routine spirometry as a preoperative evaluation for elective surgeries between January to December, 2000. Medical records were reviewed for medical history, clinical findings, smoking status, and discharge diagnoses for patients who demonstrated airflow limitation (AL), defined as FEV(1)/FVC<70% on spirometry. Of the 1031 patients who qualified for the study, 263 (26%) presented AL. Sixty-nine of these patients with AL (26%) had underlying conditions that could account for AL, such as asthma and previously diagnosed COPD. The remaining 194 patients with AL (74%) were suspected to have undiagnosed COPD, 90% of which was mild in severity. Only 30 (15%) of these patients appeared to be diagnosed have received a diagnosed as COPD by physician on this occasion. This study testifies that COPD is often unnoticed, and demonstrates that every spirometry, such as in preoperative evaluation, gives a clue to identify affected individuals, for which awareness of the disease is essential.

Pathology and pathophysiology of chronic obstructive pulmonary disease.

A variety of pathological changes have been observed in the central airways, peripheral airways and lung parenchyma of patients with chronic obstructive pulmonary disease (COPD). The characteristic changes in the central airways include inflammatory cellular infiltration into the airway wall and mucous gland enlargement. In the peripheral airways, various morphological changes are observed, including mucous plugging, epithelial abnormalities, inflammatory cellular infiltrates, fibrosis and distortion; these changes lead to airway narrowing. In the lung parenchyma, emphysema defined as alveolar destruction and airspace enlargement is present. Although the major sites of airflow limitation in patients with COPD are most likely the peripheral airways, lesions in both the peripheral airways and the lung parenchyma contribute to chronic airflow limitations.

BRONCHOPROVOCATION TESTING

Bronchoprovocation testing has been performed for more than 50 years. Challenge testing with nonselective agents has been used widely for the assessment of airflow limitation in patients, and has been used in the research setting to better characterize the pathophysiology of bronchial responsiveness. Based on this large body of literature, detailed guidelines are now available to allow for standardization of testing methodology. Such standardization is critical to achieve safe, accurate, and reproducible test results that may be interpreted meaningfully. Currently, bronchoprovocation testing with direct-acting stimuli such as methacholine is used most frequently in the clinical arena, but, in recent years, considerable interest has been developing in the use of indirect stimuli. (57) It now is recognized that bronchial hyperresponsiveness to indirect stimuli (e.g., exercise, cold air, and AMP) is highly specific for asthma and may have greater clinical relevance than does responsiveness to direct stimuli. (8) As a result, testing with indirect agents may become employed more widely in the future.

Effective delivery of particles with the HandiHaler dry powder inhalation system over a range of chronic obstructive pulmonary disease severity.

The HandiHaler is a dry powder breath activated inhaler system developed for inhalation therapy for patients with airway disease. Its operation is based on the evacuation of powder from a pierced capsule. We sought to document the inspiratory flow rates attained by patients inspiring through the HandiHaler with various degrees of airflow limitation. Subjects with stable chronic obstructive pulmonary disease (COPD) were the study's population. An in vitro study of fine particle dose was conducted using an Andersen Cascade Impactor to assess medication delivery at low inspiratory flow rates. Subsequently, an in vivo study was conducted to determine inspiratory flow rates in patients with COPD as measured through a pneumotach with a custom coupler device with and without the HandiHaler. Patients were classified into three approximately equal groups of spirometric severity ranging from mild (46-65% predicted normal forced expiratory volume in 1 sec [FEV1]), to moderate (28-45%) to severe (< or = 27%). The in vitro study indicated delivery of medication at flow rates as low as 20 L/min. Twenty-six men completed the in vivo study (age 66.9 +/- 10.9 years, FEV1 = 1.02 +/- 0.45 l.). The median peak inspiratory flow rates attained in the mild (n = 8), moderate (n = 10), and severe (n = 8) categories were 45, 45.6, and 35.4 L/min respectively. The minimum peak inspiratory flow rates in the three groups were 28.2, 21.6 and 20.4 L/min. The HandiHaler device effectively delivers particles to the lung over a wide range of airflow limitation in patients with COPD.

Persistent airflow limitation in adult-onset nonatopic asthma is associated with serologic evidence of Chlamydia pneumoniae infection

Background: Persistent airflow limitation may develop in patients with asthma, particularly in adults with nonatopic (intrinsic) disease. Although the underlying mechanisms are still unknown, respiratory infections might be involved. Objective: We investigated the annual loss of lung function in relation to seropositivity to Chlamydia pneumoniae in different subgroups of patients with severe asthma according to age at onset of asthma and atopic status. Methods: One hundred one nonsmoking outpatients with a pulmonologist’s diagnosis of severe asthma (32 men and 69 women; mean age, 46.0 years; range, 18-75 years) were included in a cross-sectional study. C pneumoniae–specific serum IgG and IgA were measured by means of ELISA. The estimated decline in lung function was calculated from the relationship between postbronchodilator FEV1/vital capacity (percent predicted) and the duration of asthma and expressed as the slope of the regression line. Results: Patients with adult-onset nonatopic asthma and positive IgG antibodies to C pneumoniae had a significantly steeper slope of the regression line compared with the other subgroups of asthmatic patients (P = .001), being indicative of a 4-fold greater estimated decline in postbronchodilator FEV1/vital capacity (2.3% vs 0.5% predicted per year of asthma duration). Conclusion: These results suggest that C pneumoniae infection might promote the development of persistent airflow limitation in patients with nonatopic adult-onset asthma. It remains to be established whether viable pathogens that are accessible for therapeutic intervention are still present in the lower airways. (J Allergy Clin Immunol 2001;107:449-54.)

570 Poor perception of airflow limitation in patients with moderate to severe asthma

570 Poor perception of airflow limitation in patients with moderate to severe asthma

Etiology, diagnosis and therapy of COPD

COPD is a disorder characterized by chronic exspiratory airflow limitation in patients with chronic bronchitis and/or emphysema. The obstruction is generally progressive, but may be partially reversible and may be accompanied by airway hyperreactivity. In this review we discuss the epidemiology, Pathophysiology, clinical features, diagnostic approaches and therapeutic management in patients with COPD. Cigarette smoking is the main risk factor for the development and progression of COPD; environmental or occupational exposure to dust or fumes and genetic factors are further contributing factors. Therefore, smoking cessation is the most important therapeutic approach. Better knowledge of neutrophilic inflammation led to the development of new drugs for the treatment of COPD. The new long-acting inhaled beta 2-agonists fundamentally improved antiobstructive therapy. They are useful to control night-time or early morning symptoms. The role of steroids and theophylline is still unclear. Their value and efficient use are discussed.

Bronchial airflow limitation and chest findings in adults with respiratory infection.

To study the predictive value of clinical chest findings for bronchial airflow limitation in patients with respiratory tract infection. Associations were analysed between FEV1 (forced expiratory volume in one second) in % of predicted and physical chest findings. The Municipal Emergency Clinic in Tromsø, Norway. 398 adult patients with respiratory tract infection and 40 general practitioners. Mean FEV1% predicted and frequency of FEV1 < 80% predicted according to chest findings. Regression coefficients of the findings with FEV % predicted as outcome variable. Mean FEV1% predicted was 87 (range 25-129). Pathological chest findings were recorded in 127 patients (32%) and in 22 of the 24 patients (92%) with FEV1% predicted less than 60. The 78 patients with wheezes had a mean FEV1% predicted of 74 (range 29-120), significantly lower than those without wheezes (p < 0.0001), and 63% had FEV1% predicted less than 80. Prolonged expiration or strenuous respiration was recorded in 49 patients. The 29 patients with wheezes in this subgroup had a significantly lower mean FEV1% predicted, 65, than the 20 patients without wheezes (p < 0.005). By multiple regression wheezes and strenuous respiration were the most significant predictors of FEV1% predicted, together with patients' statement of very annoying dyspnoea. When predicting the degree of bronchial obstruction in a patient with respiratory infection, the doctor may take into account wheezes heard by auscultation, an impression of strenuous respiration, and the patient's statement about severe dyspnoea.

Plethysmographic Parameters in the Assessment of Reversibility of Airways Obstruction in Patients With Clinical Emphysema

Slow inspiratory vital capacity (IVC) and forced expiratory volume in 1 s (FEV1) before and after an inhaled beta-agonist are widely used to detect reversible airflow limitation in patients with chronic obstructive lung disease. The measurement of airways resistance (Raw) during quiet breathing with the body plethysmograph is less frequently used. It may well be of importance in clinical emphysema where measurement of FEV1 is confounded by the collapse of the bronchi, which does not occur when measuring Raw during quiet breathing. We assessed whether Rrs, in addition to IVC and FEV1, can be used to gain a better insight into the reversibility with 400 micrograms of fenoterol in patients with clinical emphysema. We studied a group of 51 patients (9 women and 42 men; mean [+/- SD] age, 64.7 [7.7] years) who had a clinical diagnosis of emphysema. Significant reversibility was identified by spirometry (IVC, FEV1) and body plethysmography (Raw) in 20 patients (39 percent). Inspiratory vital capacity alone identified reversibility of airflow limitation in 11 patients (22 percent). In 5 patients (10 percent), the postbronchodilator improvement was seen exclusively in the Raw measurement. In the remaining patients, absence of improvement in spirometric and plethysmographic parameters was found. Subjective improvement occurred to the same extent in patients whose Raw and IVC improved. We concluded that Raw gives important information about the reversibility of airways obstruction in patients with clinical emphysema. Therefore, we suggest that tests during quiet breathing should be part of the routine examination of airways obstruction in patients with "irreversible" obstruction by conventional spirometry.

Limited Contribution of Emphysema in Advanced Chronic Obstructive Pulmonary Disease

Previous studies on autopsy specimens or surgically resected lobes or lungs have reached varying conclusions regarding the importance of small airways disease and emphysema in causing fixed expiratory airflow limitation in patients with chronic obstructive pulmonary disease (COPD). We obtained high resolution CT scans of the lung and lung function in 56 consecutive patients with fixed expiratory airflow limitation. There was poor correlation between CT emphysema score and either FEV1/FVC% (r = -0.36) or FEV1 % predicted (r = -0.20). In only 10 of the 35 patients with FEV1 < 50% predicted, the CT emphysema score was > 40, indicating significant emphysema. A strong negative correlation between diffusing capacity % predicted and diffusing capacity per alveolar volume and CT emphysema score was found only in patients with FEV1 > or = 1 L (r = -0.75, p < 0.0001). Thus, emphysema does not appear to be primarily responsible for expiratory airflow limitation in COPD. A low diffusing capacity may be spuriously misleading in patients with FEV1 < 1 L and no or trivial emphysema.

Infection-induced airway fibrosis in two rat strains with differential susceptibility.

Chronic infections play a significant role in the morbidity and mortality of patients with chronic airflow limitation. By stimulating airway inflammation, persistent infection has the potential to cause airway fibrosis. However, in patient this condition is most typically found in lungs damaged by other factors, such as smoking, abnormal secretions, or barotrauma. We report the characterization of Mycoplasma pulmonis infection-induced lung fibrosis in two immunocompetent rat strains with no preexisting lung disease. The fibrosis was predominantly in the airways, as demonstrated by the findings for infected animals of increased airway inflammation, airway fibrosis, and airway wall thickness, which correlated with the collagen content of the lungs. Also, the physiological alterations were the opposite of those found in interstitial fibrosis, with a positive correlation between lung compliance and collagen content. The airway fibrosis was noted earlier and to a greater extent in Lewis rats than in Fisher rats, and this result apparently was related to regulation of the inflammatory response. Airway wall thickness, airway inflammation, and airway fibrosis are commonly reported in tissue specimens from patients with chronic airway diseases and have been shown to correlate with airflow limitation in patients with chronic obstructive pulmonary disease. Thus, this model may be useful in furthering our understanding of the role of chronic infection and airway inflammation in airflow obstruction.

Extent of pulmonary emphysema in man and its relation to the loss of elastic recoil

1. We assessed lung density, determined by computerized tomography, as a measure of emphysema and related this to lung function and measurement of the elastic recoil of the lung in normal subjects and patients with chronic obstructive lung disease. 2. We found a significant correlation between measurements of elastic recoil pressure at 90% of total lung capacity and both the forced expiratory volume in 1 s (r = 0.80, P less than 0.001) and the transfer factor for carbon monoxide (r = 0.70, P less than 0.001). Measurements of elastic recoil of the lung also correlated with lung density as measured by computerized tomography scanning (P less than 0.001). 3. Multiple regression analysis demonstrated a correlation between the density of the lowest fifth percentile of the computerized tomography lung-density histogram, and both the natural logarithm of the shape parameter of the pressure-volume curve (P less than 0.01), and the transfer factor for carbon monoxide (P less than 0.01). However, the mean computerized tomography lung density correlated, in addition, with the elastic recoil pressure of the lungs at 90% of total lung capacity (P less than 0.001). 4. Since the elastic recoil pressure correlates with computerized tomography lung density, and hence with emphysema, and since elastic recoil pressure also correlates with the forced expiratory volume in 1 s, these results suggest that loss of elastic recoil is one determinant of airflow limitation in patients with chronic obstructive lung disease.

Assessment of reversibility of airway obstruction in patients with chronic obstructive airways disease.

Spirometry before and after an inhaled beta agonist or a course of oral prednisolone is widely used to detect reversible airflow limitation in patients with chronic obstructive lung disease. How many of these patients have a response and how the response to beta agonists relates to the response to corticosteroids is not clear. In 127 outpatients (mean (SD) FEV1 0.92 (0.38) 1) who had a clinical diagnosis of chronic obstructive lung disease (continuous breathlessness for more than six months and an FEV1/forced vital capacity (FVC) ratio less than 60%) and who appeared to be stable, the change in FEV1 was measured after salbutamol 200 micrograms from a metered dose inhaler and 5 mg from a nebuliser. Symptoms and spirometric values were recorded before and after two weeks of oral prednisolone 30 mg. Reversibility was defined as a response in FEV1 of 15% or more from baseline alone and as a 15% change and a minimum increase of at least 200 ml. The latter gave results that showed greater internal consistency between the drug regimens. On the basis of this criterion 56 patients (44%) had no response to salbutamol or prednisolone, 71 responded to salbutamol (including all 27 steroid responders), and 25 patients had a response to salbutamol 5 mg but not to 200 micrograms. In general, the largest increase in FEV1 after salbutamol occurred in the subjects with greatest improvement after prednisolone. Subjects showing a response in FEV1 after two weeks' prednisolone had a fall in total symptom score, unlike those who had no response to any treatment or a response to salbutamol only. These data show that reversibility in response to beta agonists is common in patients diagnosed on clinical grounds as having stable chronic obstructive lung disease, that it can be substantial, and that it is best detected by using a larger dose of salbutamol. Salbutamol responders were those most likely to improve after a trial of oral prednisolone. Allowance should be made for the variability of FEV1 in the calculation of the percentage response at low baseline values (less than 1 litre).

Involvement of upper-airway muscles in extrapyramidal disorders. A cause of airflow limitation.

To identify the site and cause of airflow limitation in patients with parkinsonism, we tested pulmonary function in 27 patients with extrapyramidal disorders. In 24 patients, an abnormal flow-volume loop contour, showing either regular (18 patients) or irregular (6 patients) flow oscillations, was found. On direct fiberoptic visualization of the upper airway, these oscillations corresponded to either rhythmic (4 to 8 Hz) or irregular involuntary movements of glottic and supraglottic structures. Ten patients had physiologic evidence of upper-airway obstruction, which was symptomatic in four. We conclude that the upper-airway musculature is frequently involved in extrapyramidal disorders. This causes upper-airway dysfunction that can be severe enough to limit airflow.