Natasha M. Krowchuk

Cross-Sectional Analysis of the Utility of Pulmonary Function Tests in Predicting Emphysema in Ever-Smokers

Emphysema is largely an under-diagnosed medical condition that can exist in smokers in the absence of airway obstruction. We aimed to determine the sensitivity and specificity of pulmonary function tests (PFTs) in assessing emphysema using quantitative CT scans as the reference standard. We enrolled 224 ever-smokers (current or former) over the age of 40. CT of thorax was used to quantify the low attenuation area (% emphysema), and to measure the standardized airway wall thickness. PFTs were used individually and in combination to predict their ability to discriminate radiographic emphysema. Significant emphysema (>7%) was detected in 122 (54%) subjects. Twenty six (21%) emphysema subjects had no evidence of airflow obstruction (FEV1/FVC ratio <70%), while all subjects with >23% emphysema showed airflow obstruction. The sensitivity and specificity of spirometry for detecting radiographic emphysema were 79% and 75%, respectively. Standardized airway wall thickness was increased in subjects with airflow obstruction, but did not correlate with emphysema severity. In this cohort of lifetime ever-smokers, PFTs alone were inadequate for diagnosing emphysema. Airway wall thickness quantified by CT morphometry was associated with airflow limitation, but not with emphysema indicating that the heterogeneous nature of lung disease in smokers may represent distinct phenotypes.

Knee and ankle biomechanics with lateral wedges with and without a custom arch support in those with medial knee osteoarthritis and flat feet

This study compared immediate changes in knee and ankle/subtalar biomechanics with lateral wedge orthotics with and without custom arch support in people with knee osteoarthritis and flat feet. Twenty‐six participants with radiographic evidence of medial knee osteoarthritis (22 females; age 64.0 years [SD 8.0 years], BMI 27.2 kg/m2 [4.2]) and flat feet (median foot posture index = + 5) underwent three‐dimensional gait analysis for three conditions: Control (no orthotic), lateral wedge, and lateral wedge plus arch support. Condition order was randomized. Outcomes included frontal plane knee and ankle/subtalar biomechanics, and comfort. Compared to the control, lateral wedge and lateral wedge with arch support reduced the knee adduction moment impulse by 8% and 6%, respectively (p < 0.05). However, the lateral wedge resulted in a more everted foot position (4.3 degrees) than lateral wedge plus arch support (3.2 degrees) (p < 0.05). In contrast, lateral wedge plus arch support reduced foot frontal plane excursion compared to other conditions (p < 0.05). Participants self‐reported significantly more immediate comfort with lateral wedge plus arch support compared to the control, whereas there was no difference in self‐reported comfort between lateral wedge and control. No immediate changes in knee pain were observed in any condition. Clinical significance: Rather than prescribing lateral wedges to all patients with knee osteoarthritis, those who have medial knee osteoarthritis and flat feet may prefer to use the combined orthotic to reduce loads across the knee, and to minimize the risk of foot and ankle symptoms as a consequence of orthotic treatment.

Autoreactive T Cells in Human Smokers is Predictive of Clinical Outcome

Cross-sectional studies have suggested a role for activation of adaptive immunity in smokers with emphysema, but the clinical application of these findings has not been explored. Here we examined the utility of detecting autoreactive T cells as a screening tool for emphysema in an at-risk population of smokers. We followed 156 former and current (ever)-smokers for 2 years to assess whether peripheral blood CD4 T cell cytokine responses to lung elastin fragments (EFs) could discriminate between those with and without emphysema, and to evaluate the relevance of autoreactive T cells to predict changes during follow-up in lung physiological parameters. Volunteers underwent baseline complete phenotypic assessment with pulmonary function tests, quantitative chest CT, yearly 6-min walk distance (6MWD) testing, and annual measurement of CD4 T cell cytokine responses to EFs. The areas under the receiver operating characteristic curve to predict emphysema for interferon gamma (IFN-γ), and interleukin 6 (IL-6) responses to EFs were 0.81 (95% CI of 0.74–0.88) and 0.79 (95% CI of 0.72–0.86) respectively. We developed a dual cytokine enzyme-linked immunocell spot assay, the γ-6 Spot, using CD4 T cell IFN-γ and IL-6 responses and found that it discriminated emphysema with 90% sensitivity. After adjusting for potential confounders, the presence of autoreactive T cells was predictive of a decrease in 6MWD over 2 years (decline in 6MWD, −19 m per fold change in IFN-γ; P = 0.026, and −26 m per fold change in IL-6; P = 0.003). In support of the human association studies, we cloned CD4 T cells with characteristic T helper (Th)1 and Th17 responses to EFs in the peripheral blood of ever-smokers with emphysema, confirming antigenicity of lung elastin in this population. These findings collectively suggest that the EF-specific autoreactive CD4 T cell assay, γ-6 Spot, could provide a non-invasive diagnostic tool with potential application to large-scale screening to discriminate emphysema in ever-smokers, and predict early relevant physiological outcomes in those at risk.

Qualitative and quantitative assessment of smoking-related lung disease: effect of iterative reconstruction on low-dose computed tomographic examinations.

Purpose: The purpose of this research is to examine the role that differing levels of adaptive statistical iterative reconstruction (ASIR) have on the qualitative and quantitative assessment of smoking-related lung disease. Materials and Methods: Institutional board review approval was obtained. A total of 52 patients undergoing clinically indicated low-dose computed tomographic (CT) examinations of the chest (100 kVp, 65 mAs, mean radiation dose 1.0±0.12 mSv), with reconstruction of data with different levels of blended ASIR (0%, 40%, and 100%), were consented. Qualitative assessment of CT data sets was performed by 2 trained thoracic radiologists blinded to clinical history, spirometry, and quantitative data for the presence of emphysema (%/lung zone) and the degree of respiratory bronchiolitis. Quantitative analysis was performed (Apollo Image analysis, VIDA Diagnostics) to assess emphysema and airway measures of chronic obstructive pulmonary disease. Results: The application of ASIR results in alterations in both qualitative and quantitative assessment of smoking-related lung disease. As levels of ASIR increased, both readers scored more respiratory bronchiolitis (P<0.05). At increased levels of ASIR (ie, 100% vs. 0%), the amount of emphysema measured (% below −950 HU) decreased, the number of airways measured diminished, and the airway thickness (Pi10mm) increased (P<0.001). Conclusions: The use of ASIR alters both the qualitative and quantitative assessment of smoking-related lung disease. Although a powerful tool to allow dose reduction, caution must be exercised when iterative reconstruction techniques are utilized when evaluating CT examinations for findings of chronic obstructive pulmonary disease.

Dynamic Balance Training Improves Physical Function in Individuals With Knee Osteoarthritis: A Pilot Randomized Controlled Trial

OBJECTIVE To examine the effect of a targeted balance training program on dynamic balance and self-reported physical function in people with medial tibiofemoral osteoarthritis (OA). DESIGN Single-blind randomized controlled trial. SETTING Exercise gymnasium and community dwellings. PARTICIPANTS Individuals with medial compartment knee OA (N=40). INTERVENTIONS Ten weeks of partially supervised exercises targeting dynamic balance and strength performed 4 times per week or no intervention (nonintervention group). MAIN OUTCOME MEASURES Dynamic balance was measured using the Community Balance and Mobility Scale (CB&M), and self-reported physical function was measured using the Western Ontario and McMaster Universities Arthritis Index physical function subscale. Secondary outcomes included knee pain, fear of movement, knee joint proprioception, and muscle strength. RESULTS Forty individuals underwent baseline testing, with 36 participants completing follow-up testing. Adherence to exercise in the training group was high, with 82.2% of all home-based exercise sessions completed. No significant changes were observed in any outcome in the nonintervention group at follow-up. Significant improvements in self-reported pain, physical function, and fear of movement were observed in the training group when compared with the nonintervention group. No other within- or between-group differences were observed. CONCLUSIONS A 10-week dynamic balance training program for people with knee OA significantly improved self-reported knee pain, physical function, and fear of movement; however, there was no change in dynamic balance as quantified by the CB&M. Further research is needed to investigate how exercise may result in improvement on objective measures of dynamic balance.

Lateral wedges with and without custom arch support for people with medial knee osteoarthritis and pronated feet: an exploratory randomized crossover study

BackgroundPronated foot posture is associated with many clinical and biomechanical outcomes unique to medial compartment knee osteoarthritis (OA). Though shoe-worn insole treatment, including lateral wedges, is commonly studied in this patient population, their effects on the specific subgroup of people with medial knee OA and concomitant pronated feet are unknown. The purpose of this study was to evaluate whether lateral wedge insoles with custom arch support are more beneficial than lateral wedge insoles alone for knee and foot symptoms in people with medial tibiofemoral knee osteoarthritis (OA) and pronated feet.MethodsTwenty-six people with pronated feet and symptomatic medial knee OA participated in a randomized crossover study comparing five degree lateral wedge foot insoles with and without custom foot arch support. Each intervention was worn for two months, separated by a two-month washout period of no insoles wear. Main outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function subscales, the revised short-form Foot Function Index (FFI-R) pain and stiffness subscales, and the timed stair climb test. Regression modeling was conducted to examine treatment, period, and interaction effects.ResultsTwenty-two participants completed the study, and no carryover or interaction effects were observed for any outcome. Significant treatment effects were observed for the timed stair climb, with greater improvements seen with the lateral wedges with arch support. Within-condition significant improvements were observed for WOMAC pain and physical function, as well as FFI-R pain and stiffness with lateral wedges with arch support use. More adverse effects were reported with the lateral wedges alone, while more people preferred the lateral wedges with arch support overall.ConclusionsAddition of custom arch support to a standard lateral wedge insole may improve foot and knee symptoms in people with knee OA and concomitant pronated feet. These preliminary findings suggest further research evaluating the role of shoe-worn insoles for treatment of this specific sub-group of people with knee OA is warranted.Trial registrationClinicaltrials.gov identifier: NCT02234895.

Chronic Hypoxia Accentuates Dysanaptic Lung Growth

RATIONALE Adults born and raised at high altitudes have larger lung volumes and greater pulmonary diffusion capacity compared with adults at low altitude; however, it remains unclear whether the air and tissue volumes have comparable increases and whether there is a difference in airway size. OBJECTIVES To assess the effect of chronic hypoxia on lung growth using in vivo high-resolution computed tomography measurements. METHODS Healthy adults born and raised at moderate altitude (2,000 m above sea level; n = 19) and at low altitude (400 m above sea level; n = 23) underwent high-resolution computed tomography. Differences in total lung, air, and tissue volume, mean lung density, as well as airway lumen and wall areas in anatomically matched airways were compared between groups. MEASUREMENTS AND MAIN RESULTS No significant differences for age, sex, weight, or height were found between the two groups (P > 0.05). In a multivariate regression model, altitude was a significant contributor for total lung volume (P = 0.02), air volume (P = 0.03), and tissue volume (P = 0.03), whereby the volumes were greater for the moderate- versus the low-altitude group. However, altitude was not a significant contributor for mean lung density (P = 0.35) or lumen and wall areas in anatomically matched segmental, subsegmental, and subsubsegmental airways. CONCLUSIONS Our findings suggest that the adult lung did not increase lung volume later in life by expansion of an existing number of alveoli, but rather from increased alveolarization early in life. In addition, chronic hypoxia accentuates dysanaptic lung growth by increasing the lung parenchyma but not the airways.

What are the perceptions about running and knee joint health among the public and healthcare practitioners in Canada

Objectives To evaluate the perceptions of the general public and healthcare practitioners (HCP) in Canada about the relationship between running and knee joint health, and to explore HCP`s usual recommendations to runners with knee osteoarthritis (KOA). Methods Non-runners and runners (with and without KOA) and HCP completed an online survey regarding the safety of running for knee joint health. HCP also provided information related to usual clinical recommendations. Proportions of agreement were compared between non-runners and runners. Results A total of 114 non-runners, 388 runners and 329 HCP completed the survey. Overall, running was perceived as detrimental for the knee joint by 13.1% of the general public, while 25.9% were uncertain. More uncertainty was reported regarding frequent (33.9%) and long-distance (43.6%) running. Statistical analyses revealed greater proportions of non-runners perceiving running negatively compared with runners. Overall, 48.4% believed that running in the presence of KOA would lead to disease progression, while 53.1% believed running would lead to premature arthroplasty. In HCP, 8.2%, 9.1% and 22.2% perceived that running in general, running frequently, or running long-distances are risk factors for KOA, respectively. 37.1% and 2.7% of HCP typically recommended patients with KOA to modify their running training or to quit running, respectively. Conclusion High rates of uncertainty among the general public and HCP in Canada outline the need for further studies about running and knee joint health. Filling knowledge gaps will help inform knowledge translation strategies to better orientate the general public and HCP about the safety of running for knee joint health.

Contralateral limb foot rotation during unilateral toe-in or toe-out walking in people with knee osteoarthritis

BACKGROUND Gait modification is a treatment approach often used for a variety of neuromuscular and musculoskeletal pathologies. Gait modification is commonly applied to a single limb, as is done with foot rotation (FR) in people with knee osteoarthritis (KOA). However, the extent to which gait changes observed in the trained limb are also exhibited in the untrained, contralateral limb during a training session is unknown. RESEARCH QUESTION The purpose of this study was to examine the within-limb FR differences across four unilateral FR modifications compared to natural walking. METHODS Sixteen individuals with KOA walked on a treadmill while performing four different FR conditions: 10° toe-in, 0°, 10° toe-out and 20° toe-out. Motion capture was conducted to track FR magnitude after five minutes of practice. RESULTS The change in contralateral FR angle compared to natural walking significantly increased during toe-in 10° walking (3.1°) compared to toe-out -10° and -20° walking (-1.2° and -1.5°, respectively). As expected, the ipsilateral FR angle was significantly different between all conditions. SIGNIFICANCE These results suggest that small, but statistically significant changes in the untrained contralateral limb FR are observed during FR training of the ipsilateral limb. This may indicate a desire for symmetry, or a compensation when modifying the ipsilateral limb. Therefore, clinicians may need to maintain baseline FR magnitudes in the untrained limb when a patient exhibits unilateral KOA characteristics or lateral compartment KOA.

Factor Analysis of the Community Balance and Mobility Scale in Individuals with Knee Osteoarthritis

BACKGROUND AND PURPOSE The clinical assessment of balance is an important first step in characterizing the risk of falls. The Community Balance and Mobility Scale (CB&M) is a test of balance and mobility that was designed to assess performance on advanced tasks necessary for independence in the community. However, other factors that can affect balancing ability may also be present during performance of the real-world tasks on the CB&M. It is important for clinicians to understand fully what other modifiable factors the CB&M may encompass. The purpose of this study was to evaluate the underlying constructs in the CB&M in individuals with knee osteoarthritis (OA). METHODS This was an observational study, with a single testing session. Participants with knee OA aged 50 years and older completed the CB&M, a clinical test of balance and mobility. Confirmatory factor analysis was then used to examine whether the tasks on the CB&M measure distinct factors. Three a priori theory-driven models with three (strength, balance, mobility), four (range of motion added) and six (pain and fear added) constructs were evaluated using multiple fit indices. RESULTS A total of 131 participants (mean [SD] age 66.3 [8.5] years, BMI 27.3 [5.2] kg m-2 ) participated. A three-factor model in which all tasks loaded on these three factors explained 65% of the variance and yielded the most optimal model, as determined using scree plots, chi-squared values and explained variance. The first factor accounted for 49% of the variance and was interpreted as lower limb muscle strength. The second and third factors were interpreted as mobility and balance, respectively. DISCUSSION The CB&M demonstrated the measurement of three distinct factors, interpreted as lower limb strength, balance and mobility, supporting the use of the CB&M with people with knee OA for evaluation of these important factors in falls risk and functional mobility. Copyright