Diagnosis Of Airflow Obstruction Research Articles

Preemptive Intervention in Airflow Obstruction Status Prevents the Development of Bronchiolitis Obliterans Syndrome after Allogeneic Stem Cell Transplantation: Multicenter, Prospective Phase II Study (Chiba AFO-01)

Background: Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (allo-HCT) is recognized as pulmonary chronic graft-versus-host disease (GVHD), a progressive, irreversible, and sometimes fatal complication. Periodic pulmonary function testing (PFT) for early diagnosis and timely therapeutic intervention is essential. However, effective monitoring and adequate treatment strategy for BOS have not been established. The airflow obstruction (AFO) criteria (predicted FEV1 second decreased by 5% a year or more, and FEV1-second rate <80%) had proposed to detect of a precursor of BOS, and even at AFO status, it was confirmed that increasing the risk in mortality of 2.3-fold (95% CI, 1.6- 3.3; P < 0.001) (JW Chien et al. Am J Respir Crit Care Med. 2003). In our single-center retrospective analysis, 67.2% of AFO patients progressed to BOS, and similarly, the AFO was associated with poor survival (Nakao et al., in submission). Although immunosuppressive agents, especially steroids, are usually administered or augmented for new-onset BOS, sufficient response has not necessarily been obtained. The feasibility study with inhaled fluticasone, azithromycin, and montelukast (FAM) with a brief steroid pulse had been reported, which was well tolerated; however, about one-third were a failure at 6 months, showed efficacy was extremely limited in advanced BOS. From these findings, we hypothesized that close monitoring and early intervention from the diagnosis of AFO using inhaled steroid long-acting β2-agonist budesonide/formoterol fumarate hydrate, clarithromycin, and montelukast (BCM) triplet therapy, could avert the progression to BOS. We conducted a multicenter, single-arm, open-label, prospective phase II study (Chiba AFO-01). This study was approved by the certified clinical research review board at Chiba University Hospital. (jRCTs031180338) Patients and Method: PFT was performed before and every 3 months after allo-HCT for 2 years, and from the time when the AFO criteria were met, BCM therapy was started and continued for 1 year. BOS and GVHD diagnoses were made according to the 2014 NIH Consensus Development Project on Criteria for Clinical Trials (BBMT 2015). The primary endpoint was the inhibition rate of BOS progression, and the secondary endpoints were AFO incidence rate, recurrence rate, survival rate, GVHD, intervention rate of systemic immunosuppressive therapy, and safety of BCM therapy. The statistical analysis plan considered it effective if the incidence of BOS with triple treatment was less than 65% with a two-sided P-value <0.10. Results: Between June 2016 and June 2018, 85 patients were enrolled, and 84 were included in the analysis. One was excluded from the analysis due to deviation. Fifteen of eighty-four (17.9%) met AFO criteria at the median of 178 days (63-728) after allo-HCT, and the 2-year cumulative incidence of AFO was 26.1%. Fourteen with AFO received the BCM treatment. Three patients developed BOS (0, 182, 420 days after onset of AFO). The BOS progression rate was 21.4% (95% CI: 4.7-50.8%), which was significantly below the threshold (65%) set by historical control, had demonstrated the inhibitory effect on BOS progression significantly ( P<0.001). No significant difference was observed in the relationship between AFO and primary disease, stem cell source, pretreatment, and chronic GVHD incidence compared to the non-AFO group. At the AFO diagnosis, 80% had not developed or concurrently diagnosed with chronic GVHD. During the study period, 80% had developed an active chronic GVHD in the AFO group and 54.2% in the non-AFO group. The BCM therapy was feasible, and 9 completed the treatment. Five were discontinued due to the development of IPS in 2, disease progression in 1, bacterial pneumonia in 1, and patient's preference in 1. No difference was observed between the two groups in 2-year OS (AFO 86.7% vs non-AFO 94.2%, Log-rank P=0.55) Conclusion: We revealed the target timeframe for PFT monitoring for early identifying patients at risk for subsequent BOS after allo-SCT. PFT monitoring and therapeutic intervention with BCM therapy for patients with AFO could improve outcomes. The therapeutic intervention from the BOS diagnosis is too late to improve prognosis, and early therapeutic intervention is essential when respiratory function decline is observed, regardless of the presence or absence of chronic GVHD.

Comparision of the Spirometric Measurements of Multi-National Under-graduate Medical Students from a Medical College of Central Nepal

Background: The application of pulmonary function testing is increasing in many areas of clinical medicine, including assessment of airflow limitation, diagnosis of airflow obstruction and lung restriction, evaluation of pulmonary impairment, preoperative assessment as well as public health screening. In this study, attempt has been made to evaluate Pulmonary Function Test (PFT) of healthy Nepalese young adults and compare their values with healthy Indian and Sri Lankan counterparts. Further, it tries to shed light on the correlation of these data with anthropometric parameters. 
 Methods: A total of 133 pre-clinical medical students of Manipal College of Medical Sciences were included in the study. PFT was done using a computerized automatic spirometer. 
 Results: All the pulmonary parameters showed significant gender differences. All mean value of PFT parameters were higher in males. The comparisons of different parameters of PFT according to gender between three countries namely Nepal, India and Sri Lanka showed that Nepalese and Indian females had a higher FEV1 and FVC values than Sri Lankan females (p<0.05). Sri Lankan females had lower FEV1 and FVC as compared to Nepalese and Indian females (p<0.05). However, no correlation was observed between PFTs and BMI. 
 Conclusions: Although some significant differences on PFT parameters were observed in Sri Lankan data when compared with Nepalese and Indian data, no significant difference was noticed between Nepalese and Indian values of PFT. Therefore Indian prediction equation for PFT can be used for Nepal but only after further study with a larger sample size.

Heterogeneous burden of lung disease in smokers with borderline airflow obstruction

BackgroundThe identification of smoking-related lung disease in current and former smokers with normal FEV1 is complex, leading to debate regarding using a ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) of less than 0.70 versus the predicted lower limit of normal (LLN) for diagnosis of airflow obstruction. We hypothesized that the discordant group of ever-smokers with FEV1/FVC between the LLN and 0.70 is heterogeneous, and aimed to characterize the burden of smoking-related lung disease in this group.MethodsWe compared spirometry, chest CT characteristics, and symptoms between 161 ever-smokers in the discordant group and 940 ever-smokers and 190 never-smokers with normal FEV1 and FEV1/FVC > 0.70 in the SPIROMICS cohort. We also estimated sensitivity and specificity for diagnosing objective radiographic evidence of chronic obstructive pulmonary disease (COPD) using different FEV1/FVC criteria thresholds.ResultsThe discordant group had more CT defined emphysema and non-emphysematous gas trapping, lower post-bronchodilator FEV1 and FEF25–75, and higher respiratory medication use compared with the other two groups. Within the discordant group, 44% had radiographic CT evidence of either emphysema or non-emphysematous gas trapping; an FEV1/FVC threshold of 0.70 has greater sensitivity but lower specificity compared with LLN for identifying individuals with CT abnormality.ConclusionsEver-smokers with normal FEV1 and FEV1/FVC < 0.70 but > LLN are a heterogeneous group that includes significant numbers of individuals with and without radiographic evidence of smoking-related lung disease. These findings emphasize the limitations of diagnosing COPD based on spirometric criteria alone.

Prevalence of undiagnosed airflow obstruction among people with a history of smoking in a primary care setting.

PurposeThe purpose of this study was to define the prevalence of undiagnosed airflow obstruction (AO) among subjects with a history of smoking but no previous diagnosis of chronic lung disease. The finding of AO likely represents diagnosis of chronic obstructive pulmonary disease.PatientsPeople aged ≥30 years with a history of smoking who attended public outpatient clinics for primary care services were included in this study.MethodsA cross-sectional survey in five clinics in Hong Kong using the Breathlessness, Cough, and Sputum Scale, the Lung Function Questionnaire, and office spirometry was conducted.ResultsIn total, 731 subjects (response rate =97.9%) completed the questionnaires and spirometry tests. Most of the subjects were men (92.5%) in the older age group (mean age =62.2 years; standard deviation =11.7). Of the 731 subjects, 107 had AO, giving a prevalence of 14.6% (95% confidence interval =12.1–17.2); 45 subjects with AO underwent a postbronchodilator test. By classifying the severity of chronic obstructive pulmonary disease using the Global Initiative for Chronic Obstructive Lung Disease, 27 (60%) were considered to be in mild category and 18 (40%) in moderate category. None of them belonged to the severe or very severe category. The total score of Lung Function Questionnaire showed that majority of the subjects with AO also had chronic cough, wheezing attack, or breathlessness, although most did not show any acute respiratory symptoms in accordance with the Breathlessness, Cough, and Sputum Scale. Diagnosis of AO was positively associated with the number of years of smoking (odds ratio =1.044, P=0.035) and being normal or underweight (odds ratio =1.605, P=0.046). It was negatively associated with a history of hypertension (odds ratio =0.491, P=0.003).ConclusionOne-seventh of smokers have undiagnosed AO. Spirometry screening of smokers should be considered in order to diagnose AO at an early stage, with an emphasis on smoking cessation.

Regional variations in the prevalence and misdiagnosis of air flow obstruction in China: baseline results from a prospective cohort of the China Kadoorie Biobank (CKB)

BackgroundDespite the great burden of chronic respiratory diseases in China, few large multicentre, spirometry-based studies have examined its prevalence, rate of underdiagnosis regionally or the relevance of socioeconomic and lifestyle...

Six minute walking test: an old tool with new applications

Six minute walking test: an old tool with new applications

Impulse oscillometry in comparison to spirometry in pregnant asthmatic females: Table 1—

To the Editors: Asthma complicates 3–8% of pregnancies 1, 2 and early diagnosis and optimal management of the condition seems necessary. However, spirometry as a clinical measure of airway disease mainly depends on subjects efforts during forced expiratory manoeuvres. Considering the high prevalence of respiratory symptoms and breathlessness in pregnancy and the limited functional capacity and mobility of the diaphragm because of the growing foetus 3, an easier, more rapid screening test that does not require patient cooperation would be ideal. Our study aimed to evaluate the correlation between spirometry and impulse oscillation technique (IOS) parameters to reveal the utility of IOS parameters in diagnosis of airflow obstruction in pregnant females. In total, 125 pregnant females were categorised in …

What Defines Abnormal Lung Function in Older Adults with Chronic Obstructive Pulmonary Disease?

Chronic obstructive pulmonary disease (COPD) is a very common lung disease most often related to a history of smoking. It becomes more prevalent with increasing age but remains under-diagnosed and under-treated in the elderly population. The Global Initiative for Obstructive Lung Disease (GOLD) programme has been instrumental in providing standard diagnostic criteria as well as recommendations for prevention and management of COPD. GOLD recommendations define COPD as a post-bronchodilator forced expiratory volume in 1 second (FEV(1))/forced vital capacity (FVC) of <70%, with the severity based on the value of FEV(1). This recommendation is different from that of many previous reports that have recommended diagnosing obstruction using the statistically derived lower limit of normal (LLN), which varies for each person according to age, height, ethnicity and gender. While the use of a 70% ratio may be simpler, it may result in under-diagnosis of airflow obstruction in younger people and over-diagnosis in the elderly. This is particularly important as the elderly may be most sensitive to many of the adverse effects of medications used in the treatment of COPD, including corticosteroids and anticholinergic bronchodilators.Most of the studies comparing the LLN and a fixed ratio of 70% have not been performed with post-bronchodilator testing as recommended by GOLD. Generation of post-bronchodilator reference sets and studies comparing the LLN with the post-bronchodilator FEV(1)/FVC ratio of <70% will help resolve this issue. One recent study examined patients admitted to hospitals who had an FEV(1)/FVC ratio of <70% but above the LLN, and found they were at increased risk of death and COPD complications. This would support the use of GOLD criteria. Further studies examining this population are needed.In addition to the uncertainties about what diagnostic criteria should be utilized for diagnosis of airflow obstruction, different organizations make different recommendations on screening spirometry. A conservative recommendation is to perform spirometry in symptomatic individuals. It is important to remember that while COPD is under-diagnosed in the elderly, this group is also at a higher risk of being falsely classified as having airflow obstruction using the 70% ratio recommended by GOLD. This can result in unnecessary use of medications and increased risk of adverse effects to which the elderly are more prone.

Prevalence of COPD in Women Compared to Men Around the Time of Diagnosis of Primary Lung Cancer

COPD is a well-known independent risk factor that is associated with primary lung cancer. There is, however, a striking paucity of women in studies demonstrating this association. The purpose of this study was to compare the prevalence of COPD as determined by pulmonary function tests (PFTs) between women and men at around the time of lung cancer diagnosis. We retrospectively reviewed patients with newly diagnosed primary lung cancer who had undergone PFTs prior to their treatment. The diagnosis of airflow obstruction was made according to American Thoracic Society guidelines. Comparisons of the prevalence of COPD between men and women were performed using univariate and multivariate logistic regression analysis. Of the 294 patients in the study, 151 patients (51.4%) were men and 143 patient (48.6%) were women. Of the men, 110 patients (72.8%) had COPD compared with 75 patients (52.5%) among the women. This represented a significantly lower prevalence of COPD in women than in men (odds ratio [OR], 0.41; 95% confidence interval [CI], 0.25 to 0.67; p = 0.0003). When adjusted for age and smoking status, a sustained lower prevalence of COPD was noted in women compared to men (OR, 0.44; 95% CI, 0.26 to 0.74; p = 0.002). In a subset of 256 smokers, there remained a lower prevalence of COPD in women compared to men (OR, 0.45; 95% CI, 0.27 to 0.77; p = 0.003). Adjusted analysis to control for age and number of pack-years of smoking in this subset again showed a sustained reduction in the OR for women presenting with COPD (OR, 0.48; 95% CI, 0.28 to 0.83; p = 0.009). When COPD was examined as an end point among patients who had newly diagnosed lung cancer, a significantly higher proportion of women had normal PFT results. Gender-based differences on PFT results should be considered during the screening of lung cancer, because the stratification of high-risk patients based on the presence of COPD may miss a significant proportion of women with lung cancer.

Spirometry in the Primary Care Setting

To determine if screening spirometry in the primary care setting influences the physician's diagnosis and management of obstructive lung disease. Diagnosis and management assessed before and after the intervention of screening spirometry. A total of 1,034 patients who had ever smoked and were at least 35 years of age presenting to primary care practices for any reason. Rural primary care practices. Physicians were asked prior to and following presentation of spirometry test results if they thought airflow obstruction was present and if they planned to change management based on the results. A new diagnosis of unsuspected airflow obstruction was made by the physician in 93 patients (9%), and a prior diagnosis of airflow obstruction was removed after spirometry in 115 patients (11%). After viewing the spirometry results, physicians reported that they would change patient management in 154 patients (15%). Most planned management changes occurred when airflow obstruction was newly diagnosed (57 of 93 patients, 61%) and when the diagnosis of airflow obstruction remained unchanged (80 of 195 patients, 41%). A 6-month chart review documented the addition of respiratory medications in 8% of patients. Screening spirometry influences physicians' diagnosis of airflow obstruction and management plans especially in patients with moderate-to-severe obstruction.

Multi-breath and single breath helium dilution lung volumes as a test of airway obstruction

Total lung capacity (TLC) and residual volume (RV) measurements derived from multi-breath and single breath helium dilution methods were combined to produce four indices of gas mixing: single breath volume/multi-breath volume ratio (TLCr, RVr) or multi-breath volume minus single breath volume difference (TLCd, RVd). The reproducibility of these indices and their sensitivity and specificity in discriminating between normal subjects and those with mild asthma and severe chronic obstructive pulmonary disease (COPD) was assessed. The total lung capacity ratio (TLCr) was the superior variable overall, providing a single range for both sexes with a specificity and sensitivity similar to that of the forced expiratory volume in one second (FEV1) in the diagnosis of airflow obstruction. Despite the similar sensitivity, correlation between TLCr and FEV1 was only moderate (r = 0.56). This may reflect greater influence of peripheral rather than central airflow obstruction on TLCr. Combining both tests improved sensitivity in the detection of airways obstruction in the asthmatic and COPD groups studied.

Diagnosis of airflow obstruction at high altitude.

Using predicted sea level values for spirometry done at high altitude, underestimation of airway obstruction may result. We therefore established spirometric normal values for an altitude of 3,100 m for white men.