Matthew Hegewald

Sustained Improvement With Iloprost in a COPD Patient With Severe Pulmonary Hypertension

Pulmonary hypertension is an important complication of COPD. A small subset of patients with COPD have severe pulmonary hypertension (PH) that is out of proportion to the mild increase in pulmonary arterial pressure observed commonly. Severe PH associated with COPD is associated with increased morbidity and mortality. Treatment options in this group of patients are limited with no conclusive evidence of benefit when drugs approved for treatment of pulmonary arterial hypertension are used. We describe a patient with severe PH associated with COPD who improved clinically and hemodynamically when treated with inhaled iloprost. The improvement was sustained for 2 years. Severe PH in patients with COPD needs to be recognized and novel treatment approaches considered.

Pulmonary hypertension: clinical manifestations, classification and diagnosis

Dyspnoea on exertion is the most common presenting symptom of pulmonary hypertension (PH), often a progressive and ultimately fatal condition. However, the presenting manifestations are protean, and more subtle features such hoarseness (caused by compression of the left recurrent laryngeal nerve) challenge master clinicians. Clinician scientists have refined the clinical classification in a manner that aids in accurate diagnosis and facilitates communication among healthcare providers and research investigators. Diagnostic algorithms emphasize confirmation and characterization of PH by catheterisation as well as differentiating between the current classes based upon essential and contingent diagnostic tests.

Bronchodilator Response in Patients With Normal Baseline Spirometry

BACKGROUND: Spirometry before and after bronchodilator is performed to assess air flow-limitation reversibility. In patients with normal baseline spirometry the frequency of a positive bronchodilator response, as defined by American Thoracic Society/European Respiratory Society criteria, has not been described. METHODS: We retrospectively analyzed adult patients tested in 2 academic pulmonary function testing laboratories over a 7-year period, with specific attention to patients who underwent bronchodilator testing after a normal baseline spirometry (FEV1, FVC, and FEV1/FVC within normal limits). The frequency of a positive response to bronchodilator, defined as a 12% and 200 mL increase in either FEV1 or FVC, was calculated and associated with demographic factors. RESULTS: Of the 1,394 patients with normal spirometry who were administered bronchodilator, 43 (3.1%) had a positive response. The percent of patients responding to bronchodilator were grouped according to pre-bronchodilator FEV1: > lower limit of normal to 90% of predicted = 6.9%, 90–100% of predicted = 1.9%, and > 100% of predicted = 0%. An FEV1/FVC in the lowest 2 quartiles was associated with a higher frequency of bronchodilator response. Older patients were more likely to respond to bronchodilator, but no other demographic factors were associated with a positive bronchodilator response. CONCLUSIONS: In our study population the frequency of a positive bronchodilator response in patients with normal baseline spirometry is 3.1%. None of the patients with a pre-bronchodilator FEV1 > 100% of predicted and only 1.9% of patients with an FEV1 between 90% and 100% of predicted responded. Bronchodilator testing can be omitted in patients with normal spirometry and an FEV1 above 90% of predicted, as they have a low probability of a positive response.

Spirometric reference values for Malagasy adults aged 18–73 years

The American Thoracic Society (ATS) and European Respiratory Society (ERS) recommend that spirometry prediction equations be derived from samples of similar race/ethnicity. Malagasy prediction equations do not exist. The objectives of this study were to establish prediction equations for healthy Malagasy adults, and then compare Malagasy measurements with published prediction equations. We enrolled 2491 healthy Malagasy subjects aged 18–73 years (1428 males) from June 2006 to April 2008. The subjects attempted to meet the ATS/ERS 2005 guidelines when performing forced expiratory spirograms. We compared Malagasy measurements of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with predictions from the European Community for Steel and Coal (ECSC), the third National Health and Nutrition Examination Survey (NHANES III) and the ERS Global Lung Function Initiative (GLI) 2012 study. A linear model for the entire population, using age and height as independent variables, best predicted all spirometry parameters for sea level and highland subjects. FEV1, FVC and FEV1/FVC were most accurately predicted by NHANES III African-American male and female, and by GLI 2012 black male and black and South East Asian female equations. ECSC-predicted FEV1, FVC and FEV1/FVC were poorly matched to Malagasy measurements. We provide the first spirometry reference equations for a healthy adult Malagasy population, and the first comparison of Malagasy population measurements with ECSC, NHANES III and GLI 2012 prediction equations. Malagasy linear regression predicts spirometry, as do NHANES III and GLI 2012 black and South East Asian equations http://ow.ly/DvUQv

Prevalence of Airway Obstruction in Recreational SCUBA Divers

Abstract Objective.—The prevalence of airflow obstruction in recreational self-contained underwater breathing apparatus (SCUBA) divers is unknown. Since airflow obstruction is a relative contraindication for diving, we conducted a study to determine its prevalence and magnitude in a cohort of recreational divers in Saba, Netherlands Antilles. Methods.—Prior to diving, divers were asked to complete a diving/health questionnaire and then to perform spirometry administered by trained dive store personnel. Spirometry instrumentation provided immediate feedback regarding test quality. Results.—Of 8365 eligible divers during the study period (November 1997–March 1999), 668 enrolled and completed questionnaires. Of those completing questionnaires, 46% reported a history of smoking, 13% were current smokers, 15% wheezed, 6% had asthma, 4% used bronchodilators, and 3% took oral steroids. Of 654 completing spirometry, 231 had acceptable spirometry quality and complete questionnaires. By forced expiratory volume in 1 second/forced vital capacity, 10% had mild, 1.7% had moderate, and 0.4% had severe airflow obstruction. Conclusions.—The prevalence of airflow obstruction was 6% to 15% by report and 12% by spirometry, approximating the combined prevalence of asthma and chronic obstructive pulmonary disease in the general population. Study limitations include possible self-selection and low enrollment rate. Prospective lung function testing can be conducted at remote sites using nonmedical personnel as “testers.” This study could guide future investigations to determine if asthma is a risk factor for decompression illness.

Comparison of NHANES III and ERS/GLI 12 for airway obstruction classification and severity

The diagnosis and severity categorisation of obstructive lung disease is determined using reference values. The American Thoracic Society/European Respiratory Society in 2005 recommended the National Health and Nutrition Examination Survey (NHANES) III spirometry prediction equations for patients in USA aged 8–80 years. The Global Lung Initiative 2012 (GLI 12) provided spirometry prediction equations for patients aged 3–95 years. Comparison of the NHANES III and GLI 12 prediction equations for diagnosing and categorising airway obstruction in patients in USA has not been made. We aimed to quantify the differences between NHANES III and GLI 12 predicted values in Caucasians aged 18–95 years, using both mathematical simulation and clinical data. We compared predicted forced expiratory volume in 1 s (FEV1) and lower limit of normal (LLN) FEV1/forced vital capacity (FVC) % for NHANES III and GLI 12 prediction equations by applying both a simulation model and clinical spirometry data to quantify differences in the diagnosis and categorisation of airway obstruction. Mathematical simulation revealed significant similarities and differences between prediction equations for both LLN FEV1/FVC % and predicted FEV1. There are significant differences when using GLI 12 and NHANES III to diagnose airway obstruction and severity in Caucasian patients aged 18–95 years. Similarities and differences exist between NHANES III and GLI 12 for some age and height combinations. The differences in LLN FEV1/FVC % and predicted FEV1 are most prominent in older taller/shorter individuals. The magnitude of the differences can be large and may result in differences in clinical management. Significant differences exist between NHANES III and GLI 12 prediction equations for some age and height combinations http://ow.ly/4mWTZ8

Single-Breath Diffusing Capacity for Carbon Monoxide Instrument Accuracy Across 3 Health Systems

BACKGROUND: Measuring diffusing capacity of the lung for carbon monoxide (DLCO) is complex and associated with wide intra- and inter-laboratory variability. Increased DLCO variability may have important clinical consequences. The objective of the study was to assess instrument performance across hospital pulmonary function testing laboratories using a DLCO simulator that produces precise and repeatable DLCO values. METHODS: DLCO instruments were tested with CO gas concentrations representing medium and high range DLCO values. The absolute difference between observed and target DLCO value was used to determine measurement accuracy; accuracy was defined as an average deviation from the target value of < 2.0 mL/min/mm Hg. Accuracy of inspired volume measurement and gas sensors were also determined. RESULTS: Twenty-three instruments were tested across 3 healthcare systems. The mean absolute deviation from the target value was 1.80 mL/min/mm Hg (range 0.24–4.23) with 10 of 23 instruments (43%) being inaccurate. High volume laboratories performed better than low volume laboratories, although the difference was not significant. There was no significant difference among the instruments by manufacturers. Inspired volume was not accurate in 48% of devices; mean absolute deviation from target value was 3.7%. Instrument gas analyzers performed adequately in all instruments. CONCLUSIONS: DLCO instrument accuracy was unacceptable in 43% of devices. Instrument inaccuracy can be primarily attributed to errors in inspired volume measurement and not gas analyzer performance. DLCO instrument performance may be improved by regular testing with a simulator. Caution should be used when comparing DLCO results reported from different laboratories.

Long-term intersession variability for single-breath diffusing capacity

Background: Characterizing long-term diffusing capacity (D<smlcap>l</smlcap>_CO) variability is important in assessing quality control for D<smlcap>l</smlcap>_CO equipment and patient management. Long-term D<smlcap>l</smlcap>_CO variability has not been reported. Objectives: It was the aim of this study to characterize long-term variability of D<smlcap>l</smlcap>_CO in a cohort of biocontrols and to compare different methods of selecting a target value. Methods: Longitudinal D<smlcap>l</smlcap>_CO monitoring of biocontrols was performed as part of the inhaled insulin development program; 288 biocontrols were tested twice monthly for up to 5 years using a standardized technique. Variability, expressed either as percent change or D<smlcap>l</smlcap>_CO units, was assessed using three different target values. Results: The 90th percentile for mean intersession change in D<smlcap>l</smlcap>_CO was between 10.9 and 15.8% (2.6–4.1 units) depending on the target value. Variability was lowest when the mean of all D<smlcap>l</smlcap>_CO tests was used as the target value and highest when the baseline D<smlcap>l</smlcap>_CO was used. The average of the first six D<smlcap>l</smlcap>_CO tests provided an accurate estimate of the mean D<smlcap>l</smlcap>_CO value. Using this target, the 90th percentile for mean intersession change was 12.3% and 3.0 units. Variability was stable over time and there were no meaningful associations between variability and demographic factors. Conclusions: D<smlcap>l</smlcap>_CO biocontrol deviations >12% or >3.0 units, from the average of the first six tests, indicate that the instrument is not within quality control limits and should be carefully evaluated before further patient testing.

Airflow Obstruction Categorization Methods and Mortality

Rationale: Current guidelines recommend using forced expiratory volume in 1 second (FEV1) % predicted to categorize the severity of airflow obstruction. There are limitations to using FEV1 % predicted for this purpose, including bias associated with demographic factors and the inability to correct for “lung size.” Other methods for grading the severity of airflow obstruction have been proposed to address these limitations. Objectives: Our objectives were to categorize airflow obstruction severity using these methods and then determine which method results in a categorization most closely associated with mortality. Methods: Study subjects were patients aged 40‐80 years tested in our pulmonary function test laboratories in the period 2002 to 2013 with airflow obstruction based on an FEV1/forced vital capacity (FVC) less than the lower limit of normal. Categorization of airflow obstruction severity was determined using four methods: FEV1 % predicted; FEV1 % predicted adjusted by FVC % predicted; FEV1/FVC confidence interval approach; and FEV1 z‐scores. Receiver operating characteristic curve analysis was used to determine which categorization method best predicts 5‐year survival. Results: We identified 2,000 patients with airflow obstruction. Important differences in the categorization of airflow obstruction severity were observed using the different methods. More patients were categorized as having severe obstruction using FEV1 % predicted and FEV1 z‐scores compared with FEV1 % predicted adjusted by FVC % predicted and FEV1/FVC confidence interval approach. FEV1 % predicted was the best predictor of 5‐year survival among the four methods studied. Conclusions: In our study, categorizing airflow obstruction severity using FEV1 % predicted best predicted 5‐year survival. This validates the current guideline recommendation that FEV1 % predicted be used to categorize the severity of airflow obstruction.

Evaluating How Post-Bronchodilator Vital Capacities Affect the Diagnosis of Obstruction in Pulmonary Function Tests

BACKGROUND: Although the ratio of FEV1 to the vital capacity (VC) is universally accepted as the cornerstone of pulmonary function test (PFT) interpretation, FVC remains in common use. We sought to determine what the differences in PFT interpretation were when the largest measured vital capacity (VCmax) was used instead of the FVC. METHODS: We included 12,238 consecutive PFTs obtained for routine clinical care. We interpreted all PFTs first using FVC in the interpretation algorithm and then again using the VCmax, obtained either before or after administration of inhaled bronchodilator. RESULTS: Six percent of PFTs had an interpretive change when VCmax was used instead of FVC. The most common changes were: new diagnosis of obstruction and exclusion of restriction (previously suggested by low FVC without total lung capacity measured by body plethysmography). A nonspecific pattern occurred in 3% of all PFT interpretations with FVC. One fifth of these 3% produced a new diagnosis of obstruction with VCmax. The largest factors predicting a change in PFT interpretation with VCmax were a positive bronchodilator response and the administration of a bronchodilator. Larger FVCs decreased the odds of PFT interpretation change. Surprisingly, the increased numbers of PFT tests did not increase odds of PFT interpretation change. CONCLUSIONS: Six percent of PFTs have a different interpretation when VCmax is used instead of FVC. Evaluating borderline or ambiguous PFTs using the VCmax may be informative in diagnosing obstruction and excluding restriction.