Prevalence, stability, and clinical significance of an isolated low FEV1 spirometry pattern in children.

OBJECTIVES: In adults, an isolated low FEV1 pattern (an FEV1 below the lower limit of normal with a preserved FVC and FEV1/FVC) has been associated with the risk of developing airway obstruction. Our objective was to examine the prevalence, stability, and clinical significance of an isolated low FEV1 pattern in the pediatric population. METHODS: We conducted a retrospective study of spirometries from children ages 6-21 years and categorized tests into spirometry patterns according to published guidelines and recent literature. In a subgroup of tests with an isolated low FEV1 pattern, we evaluated spirometry technique. We also examined the association of having a test with an isolated low FEV1 pattern with clinical markers of disease severity in a subgroup of children with cystic fibrosis (CF). RESULTS: The isolated low FEV1 pattern was uncommon across the 29,979 tests included (n = 645 [2%]). In the 263 children with an isolated low FEV1 pattern who had a follow-up test performed, the most frequent spirometry pattern at last test was normal (n = 123 [47%]). A primary diagnosis of CF was associated with increased odds of having at least one test with an isolated low FEV1 pattern (OR = 8.37, 95% CI = 4.70-15.96, p < .001). The spirometry quality in a subgroup of tests with an isolated low FEV1 pattern (n = 50) was satisfactory. In the subgroup of children with CF (n = 102), those who had a test with an isolated low FEV1 pattern had higher odds of using oral antibiotics in the last 12 months than those who had a normal pattern (OR = 3.50, 95% CI = 1.15-10.63, p = .03). CONCLUSIONS: The isolated low FEV1 pattern can occur repeatedly over time, usually transitions to a normal pattern, is not due to a poor spirometry technique, and could be clinically relevant in children with chronic lung diseases.

Measurement of pulmonary transit time and estimation of pulmonary blood volume after exercise using contrast echocardiography.

BACKGROUND: Pulmonary transit time (PTT) and pulmonary blood volume (PBV) derived from non-invasive imaging correlate with pulmonary artery wedge pressure. The response of PBV to exercise may be useful in the evaluation of cardiopulmonary disease but whether PBV can be obtained reliably following exercise is unknown. We therefore aimed to assess the technical feasibility of measuring PTT and PBV after exercise using contrast echocardiography. METHODS: In healthy volunteers, PTT was calculated from time-intensity curves generated as contrast traversed the cardiac chambers before and immediately after participants performed sub-maximal exercise on the Standard Bruce Protocol. From the product of PTT and heart rate (HR) during contrast passage through the pulmonary circulation, PBV relative to systemic stroke volume (rPBV) was calculated. RESULTS: The cohort consisted of 14 individuals (age: 46 ± 8 years; 2 female) without cardiopulmonary disease. Exercise time was 8 ¾ ± 1 ¾ minutes and participants reached 85 ± 9% of age-predicted maximal HR, which corresponded to a near-doubling of resting HR at the time of post-exercise contrast injection. Data sufficient to derive PTT and rPBV were obtained for all participants. With exercise, the change in PBV from baseline ranged from 56 to 138% of systemic stroke volume, consistent with rPBV and absolute PBV values obtained in prior studies. CONCLUSIONS: Acquisition of PTT and rPBV using contrast echocardiography after exercise is achievable and the results are physiologically plausible. As the next step towards clinical implementation, validation of this technique against hemodynamic exercise studies appears reasonable.

Physiologic responses to exercise in survivors of critical illness: an exploratory pilot study.

BACKGROUND: ICU survivors suffer from impaired physical function and reduced exercise capacity, yet the underlying mechanisms are poorly understood. The goal of this exploratory pilot study was to investigate potential mechanisms of exercise limitation using cardiopulmonary exercise testing (CPET) and 6-min walk testing (6MWT). METHODS: We enrolled adults aged 18 years or older who were treated for respiratory failure or shock in medical, surgical, or trauma ICUs at Vanderbilt University Medical Center (Nashville, TN, United States). We excluded patients with pre-existing cardiac dysfunction, a contraindication to CPET, or the need for supplemental oxygen at rest. We performed CPET and 6MWT 6 months after ICU discharge. We measured standard CPET parameters in addition to two measures of oxygen utilization during exercise (VO2-work rate slope and VO2 recovery half-time). RESULTS: We recruited 14 participants. Low exercise capacity (i.e., VO2Peak < 80% predicted) was present in 11 out of 14 (79%) with a median VO2Peak of 12.6 ml/kg/min [9.6-15.1] and 6MWT distance of 294 m [240-433]. In addition to low VO2Peak, CPET findings in survivors included low oxygen uptake efficiency slope, low oxygen pulse, elevated chronotropic index, low VO2-work rate slope, and prolonged VO2 recovery half-time, indicating impaired oxygen utilization with a hyperdynamic heart rate and ventilatory response, a pattern seen in non-critically ill patients with mitochondrial myopathies. Worse VO2-work rate slope and VO2 recovery half-time were strongly correlated with worse VO2Peak and 6MWT distance, suggesting that exercise capacity was potentially limited by impaired muscle oxygen utilization. CONCLUSIONS: These exploratory data suggest ICU survivors may suffer from impaired muscular oxygen metabolism due to mitochondrial dysfunction that impairs exercise capacity long-term. These findings should be further characterized in future studies that include direct assessments of muscle mitochondrial function in ICU survivors.

Anaplastic Large Cell Lymphoma Manifesting as Pleural Effusion in a Patient with Long-Standing Eosinophilia.

Anaplastic large cell lymphoma (ALCL) is a lymphoma of T-cell origin, characterized by the presence of large lymphoid cells with abundant cytoplasm and pleomorphic, often horseshoe-shaped nuclei (hallmark cells), as well as strong and uniform expression of cluster of differentiation (CD)30. Two distinct clinicopathologic categories of ALCL include primary cutaneous ALCL and systemic ALCL. Systemic ALCL is further classified into anaplastic lymphoma kinase (ALK)-positive, ALK-negative, and breast implant-associated ALCL. Most ALCLs occurring in adults are ALK negative and present in lymph nodes rather than extranodal sites.Primary diagnosis of ALCL in the pleural fluid is extremely rare, with no convincing recent reports available that are based in current understanding of this entity. Herein, we describe a well-characterized case of ALK-negative ALCL with no rearrangement but amplification of DUSP22/IRF4, diagnosed by cytologic examination of the pleural effusion in a 68-year-old white man with a 3-year history of unexplained eosinophilia and pulmonary infiltrates. Also, we present a review of the literature and discuss the current understanding of ALCL based on the 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms.

Interstitial Pneumonia With Autoimmune Features: An Emerging Challenge at the Intersection of Rheumatology and Pulmonology.

Interstitial lung disease (ILD) remains a cause of significant morbidity and mortality in patients with connective tissue disease (CTD)-associated ILD. While some patients meet clear classification criteria for a systemic rheumatic disease, a subset of patients do not meet classification criteria but still benefit from immunosuppressive therapy. In 2015, the American Thoracic Society and European Respiratory Society described classification criteria for interstitial pneumonia with autoimmune features (IPAF) to identify patients with lung-predominant CTD who lack sufficient features of a systemic rheumatic disease to meet classification criteria. Although these criteria are imperfect, they are an important attempt to classify the patient with undifferentiated disease for future study. Rheumatologists play a key role in the evaluation of potential IPAF in patients, especially as many patients with a myositis-spectrum disease (e.g., non-Jo-1 antisynthetase syndrome, anti-melanoma differentiation-associated protein 5 antibody inflammatory myositis, or anti-PM/Scl antibody-associated inflammatory myositis) would be classified under IPAF using the currently available criteria for inflammatory myositis, and would therefore benefit from rheumatologic comanagement. The aim of this review was to describe the historical context that led to the development of these criteria and to discuss the limitations of the current criteria, diagnostic challenges, treatment options, and strategies for disease monitoring.

Exercise right heart catheterization for pulmonary hypertension identified on screening echocardiography in adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort.

Pulmonary hypertension, determined noninvasively by tricuspid regurgitant jet velocity on Doppler echocardiography, was previously identified in 25% of long-term survivors who received chest-directed radiotherapy. To validate noninvasively defined pulmonary hypertension, survivors (mean age 48 years), exposed to chest radiotherapy, underwent right heart catheterization with planned cardiopulmonary exercise testing during catheterization. Eight participants had an elevated mean pulmonary artery pressure at rest (≥25 mm Hg) or with subsequent exercise (>30 mm Hg), evidence of hemodynamically confirmed pulmonary hypertension by right heart catheterization. Cardiopulmonary exercise testing further defined the magnitude and etiology of cardiopulmonary limitations in this life-threatening late effect.

Constrictive bronchiolitis in soldiers returning from Iraq and Afghanistan.

BACKGROUND: In this descriptive case series, 80 soldiers from Fort Campbell, Kentucky, with inhalational exposures during service in Iraq and Afghanistan were evaluated for dyspnea on exertion that prevented them from meeting the U.S. Army's standards for physical fitness. METHODS: The soldiers underwent extensive evaluation of their medical and exposure history, physical examination, pulmonary-function testing, and high-resolution computed tomography (CT). A total of 49 soldiers underwent thoracoscopic lung biopsy after noninvasive evaluation did not provide an explanation for their symptoms. Data on cardiopulmonary-exercise and pulmonary-function testing were compared with data obtained from historical military control subjects. RESULTS: Among the soldiers who were referred for evaluation, a history of inhalational exposure to a 2003 sulfur-mine fire in Iraq was common but not universal. Of the 49 soldiers who underwent lung biopsy, all biopsy samples were abnormal, with 38 soldiers having changes that were diagnostic of constrictive bronchiolitis. In the remaining 11 soldiers, diagnoses other than constrictive bronchiolitis that could explain the presenting dyspnea were established. All soldiers with constrictive bronchiolitis had normal results on chest radiography, but about one quarter were found to have mosaic air trapping or centrilobular nodules on chest CT. The results of pulmonary-function and cardiopulmonary-exercise testing were generally within normal population limits but were inferior to those of the military control subjects. CONCLUSIONS: In 49 previously healthy soldiers with unexplained exertional dyspnea and diminished exercise tolerance after deployment, an analysis of biopsy samples showed diffuse constrictive bronchiolitis, which was possibly associated with inhalational exposure, in 38 soldiers.

Exercise-induced pulmonary arterial hypertension.

BACKGROUND: The clinical relevance of exercise-induced pulmonary arterial hypertension (PAH) is uncertain, and its existence has never been well studied by direct measurements of central hemodynamics. Using invasive cardiopulmonary exercise testing, we hypothesized that exercise-induced PAH represents a symptomatic stage of PAH, physiologically intermediate between resting pulmonary arterial hypertension and normal. METHODS AND RESULTS: A total of 406 consecutive clinically indicated cardiopulmonary exercise tests with radial and pulmonary arterial catheters and radionuclide ventriculographic scanning were analyzed. The invasive hemodynamic phenotype of exercise-induced PAH (n=78) was compared with resting PAH (n=15) and normals (n=16). Log-log plots of mean pulmonary artery pressure versus oxygen uptake (V(.)o(2)) were obtained, and a "join-point" for a least residual sum of squares for 2 straight-line segments (slopes m1, m2) was determined; m2m1="takeoff" pattern. At maximum exercise, V(.)o(2) (55.8+/-20.3% versus 66.5+/-16.3% versus 91.7+/-13.7% predicted) was lowest in resting PAH, intermediate in exercise-induced PAH, and highest in normals, whereas mean pulmonary artery pressure (48.4+/-11.1 versus 36.6+/-5.7 versus 27.4+3.7 mm Hg) and pulmonary vascular resistance (294+/-158 versus 161+/-60 versus 62+/-20 dyne x s x cm(-5), respectively; P<0.05) followed an opposite pattern. An exercise-induced PAH plateau (n=32) was associated with lower o(2)max (60.6+/-15.1% versus 72.0+/-16.1% predicted) and maximum cardiac output (78.2+/-17.1% versus 87.8+/-18.3% predicted) and a higher resting pulmonary vascular resistance (247+/-101 versus 199+/-56 dyne x s x cm(-5); P<0.05) than takeoff (n=40). The plateau pattern was most common in resting PAH, and the takeoff pattern was present in nearly all normals. CONCLUSIONS: Exercise-induced PAH is an early, mild, and clinically relevant phase of the PAH spectrum.