PURPOSE: Before the end of the 20th century, American Indians (AIs) primarily resided in nonmetropolitan areas. Shifting demographic trends have led to a majority of AIs now living in urban areas, leading to new health care barriers for AIs. AIs experience the poorest survival from all cancers combined compared to all other racial groups. Identifying and classifying barriers to cancer care may facilitate supportive interventions and programs to improve access and treatment. METHODS: A 5-year cancer symptom management project targeted AIs in the Southwest. The first phase of the randomized clinical trial consisted of 13 focus groups (N = 126) of cancer patients/survivors and their caregivers. Discussions explored existing and perceived barriers and facilitators to cancer symptom management and cancer treatment. FINDINGS: Significant barriers to cancer-related care were found among urban AIs, as compared to their rural counterparts. Barriers were classified within 4 subgroups: (1) structural, (2) physical, (3) supportive, or (4) cultural. Urban AIs reported barriers that are both structural and physical (inadequate access to care and public transportation) and supportive (lack of support, resources and technology, and less access to traditional healing). Rural participants reported communication and culture barriers (language differences, illness beliefs, and low levels of cancer care knowledge), as well as unique structural, physical, and supportive barriers. CONCLUSION: It is important to identify and understand culturally and geographically influenced barriers to cancer treatment and symptom management. We provide recommendations for strategies to reduce health disparities for AIs that are appropriate to their region of residence and barrier type.

Purpose of review

Interstitial lung disease (ILD) is comprised of a heterogeneous group of disorders with highly variable natural histories and response to therapies. Pharmacogenetics focuses on the variability in drug response because of the presence of genetic factors that influence drug metabolism or disease activity. In this article, we review relevant drug-specific and disease-specific polymorphisms that may influence therapeutic response, and then highlight a recently identified drug-gene interaction in patients with idiopathic pulmonary fibrosis (IPF).

Recent findings

The emergence of high-throughput genomic technology has allowed for identification of gene polymorphisms associated with susceptibility to specific disease states, including IPF and several connective tissue diseases known to cause ILD. IPF risk loci span a diverse group of genes, while most associated with connective tissue disease are critical to immune signaling. A recent pharmacogenetic analysis of patients enrolled in an IPF clinical trial identified a variant within TOLLIP to be associated with differential response to N-acetylcysteine therapy.

Summary

Though few pharmacogenetic investigations have been conducted in patients with ILD to date, ample opportunities for pharmacogenetic exploration exist in this patient population. Such exploration will advance our understanding of specific ILDs and help usher in an era of personalized medicine.

Purpose

Before the end of the 20th century, American Indians (AIs) primarily resided in nonmetropolitan areas. Shifting demographic trends have led to a majority of AIs now living in urban areas, leading to new health care barriers for AIs. AIs experience the poorest survival from all cancers combined compared to all other racial groups. Identifying and classifying barriers to cancer care may facilitate supportive interventions and programs to improve access and treatment.

Methods

A 5-year cancer symptom management project targeted AIs in the Southwest. The first phase of the randomized clinical trial consisted of 13 focus groups (N = 126) of cancer patients/survivors and their caregivers. Discussions explored existing and perceived barriers and facilitators to cancer symptom management and cancer treatment.

Findings

Significant barriers to cancer-related care were found among urban AIs, as compared to their rural counterparts. Barriers were classified within 4 subgroups: (1) structural, (2) physical, (3) supportive, or (4) cultural. Urban AIs reported barriers that are both structural and physical (inadequate access to care and public transportation) and supportive (lack of support, resources and technology, and less access to traditional healing). Rural participants reported communication and culture barriers (language differences, illness beliefs, and low levels of cancer care knowledge), as well as unique structural, physical, and supportive barriers.

Conclusion

It is important to identify and understand culturally and geographically influenced barriers to cancer treatment and symptom management. We provide recommendations for strategies to reduce health disparities for AIs that are appropriate to their region of residence and barrier type.

Study objectives

Obstructive sleep apnea (OSA) is defined by pauses in breathing during sleep, but daytime breathing dysregulation may also be present. Sleep may unmask breathing instability in OSA that is usually masked by behavioral influences during wakefulness. A breath-hold (BH) challenge has been used to demonstrate breathing instability. One measure of breathing stability is breathing rate variability (BRV). We aimed to assess BRV during rest and in response to BH in OSA.

Methods

We studied 62 participants (31 with untreated OSA: respiratory event index [mean ± SD] 20 ± 15 events/h, 12 females, age 51 ± 14 years, body mass index [BMI] 32 ± 8 kg/m²; 31 controls: 17 females, age 47 ± 13 years; BMI 26 ± 4 kg/m²). Breathing movements were collected using a chest belt for 5 minutes of rest and during a BH protocol (60 seconds baseline, 30 seconds BH, 90 seconds recovery, 3 repeats). From the breathing movements, we calculated median breathing rate (BR) and interquartile BRV at rest. We calculated change in BRV during BH recovery from baseline. Group comparisons of OSA vs control were conducted using analysis of covariance with age, sex, and BMI as covariates.

Results

We found 10% higher BRV in OSA vs controls (P < .05) during rest. In response to BH, BRV increased 7% in OSA vs 1% in controls (P < .001). Resting BR was not significantly different in OSA and controls, and sex and age did not have any significant interaction effects. BMI was associated with BR at rest (P < .05) and change in BRV with BH (P < .001), but no significant BMI-by-group interaction effect was observed.

Conclusions

The findings suggest breathing instability as reflected by BRV is high in OSA during wakefulness, both at rest and in response to a stimulus. Breathing instability together with high blood pressure variability in OSA may reflect a compromised cardiorespiratory consequence in OSA during wakefulness.

Citation

Pal A, Martinez F, Akey MA, et al. Breathing rate variability in obstructive sleep apnea during wakefulness. J Clin Sleep Med. 2022;18(3):825-833.

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive deposition of extracellular matrix, worsening dyspnea, and eventual mortality. Pathogenesis of IPF is poorly understood and the role inflammation and activated leukocytes play in the disease process is controversial. Previous studies demonstrated that activated leukocyte subsets characterize IPF patients. We sought to validate this observation in a well-defined cohort of 35 IPF patients and to correlate the observed leukocyte phenotypes with robust parameters of disease progression. We demonstrate that in univariate and multivariate analyses, increases in the CD14hi, CD16hi subset of monocytes measured at baseline correlated with disease progression, with a threshold value >0.5% of the total peripheral blood mononuclear cells being a significant predictor for worse outcome. In addition, several T cell subsets, including CD25 expressing CD4 cells, and CXCR3 expressing CD4 and CD8 subsets correlated with disease progression when found in increased percentages in the peripheral blood of IPF patients when sampled at baseline. Somewhat surprising in comparison to previous literature, the CD4 T cells did not appear to have lost expression of the co-stimulatory molecule, CD28, but the CD8 T cells did. Taken together, these results are consistent with the presence of an inflammatory process in IPF patients who eventually progress. However, when longitudinal measurements of these same markers were examined, there was significant heterogeneity of expression and these biomarkers did not necessarily remain elevated in IPF patients with progressive disease. We interpret this heterogeneity to suggest that IPF patients experience episodic inflammatory events that once triggered, may lead to disease progression. This longitudinal heterogeneity in biomarker analyses may explain why such markers are not consistently measured in all IPF cohorts.

Background

Acetylcysteine has been suggested as a beneficial treatment for idiopathic pulmonary fibrosis, although data from placebo-controlled studies are lacking.

Methods

In our initial double-blind, placebo-controlled trial, we randomly assigned patients who had idiopathic pulmonary fibrosis with mild-to-moderate impairment in pulmonary function to receive a three-drug regimen of prednisone, azathioprine, and acetylcysteine; acetylcysteine alone; or placebo. The study was interrupted owing to safety concerns associated with the three-drug regimen. The trial continued as a two-group study (acetylcysteine vs. placebo) without other changes; 133 and 131 patients were enrolled in the acetylcysteine and placebo groups, respectively. The primary outcome was the change in forced vital capacity (FVC) over a 60-week period.

Results

At 60 weeks, there was no significant difference in the change in FVC between the acetylcysteine group and the placebo group (-0.18 liters and -0.19 liters, respectively; P=0.77). In addition, there were no significant differences between the acetylcysteine group and the placebo group in the rates of death (4.9% vs. 2.5%, P=0.30 by the log-rank test) or acute exacerbation (2.3% in each group, P>0.99).

Conclusions

As compared with placebo, acetylcysteine offered no significant benefit with respect to the preservation of FVC in patients with idiopathic pulmonary fibrosis with mild-to-moderate impairment in lung function. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00650091.).

Chronic obstructive pulmonary disease (COPD) is a common, complex, and heterogeneous disorder that is responsible for substantial and growing morbidity, mortality, and health-care expense worldwide. Of imperative importance to decipher the complexity of COPD is to identify groups of patients with similar clinical characteristics, prognosis, or therapeutic needs, the so-called clinical phenotypes. This strategy is logical for research but might be of little clinical value because clinical phenotypes can overlap in the same patient and the same clinical phenotype could result from different biological mechanisms. With the goal to match assessment with treatment choices, the latest iteration of guidelines from the Global Initiative for Chronic Obstructive Lung Disease reorganised treatment objectives into two categories: to improve symptoms (ie, dyspnoea and health status) and to decrease future risk (as predicted by forced expiratory volume in 1 s level and exacerbations history). This change thus moves treatment closer to individualised medicine with available bronchodilators and anti-inflammatory drugs. Yet, future treatment options are likely to include targeting endotypes that represent subtypes of patients defined by a distinct pathophysiological mechanism. Specific biomarkers of these endotypes would be particularly useful in clinical practice, especially in patients in which clinical phenotype alone is insufficient to identify the underlying endotype. A few series of potential COPD endotypes and biomarkers have been suggested. Empirical knowledge will be gained from proof-of-concept trials in COPD with emerging drugs that target specific inflammatory pathways. In every instance, specific endotype and biomarker efforts will probably be needed for the success of these trials, because the pathways are likely to be operative in only a subset of patients. Network analysis of human diseases offers the possibility to improve understanding of disease pathobiological complexity and to help with the development of new treatment alternatives and, importantly, a reclassification of complex diseases. All these developments should pave the way towards personalised treatment of patients with COPD in the clinic.

Background: Inspiratory muscle training (IMT) may improve respiratory and cardiovascular functions in obstructive sleep apnea (OSA) and is a potential alternative or adjunct treatment to continuous positive airway pressure (CPAP). IMT protocols were originally designed for athletes, however, we found some OSA patients could not perform the exercise, so we aimed for a more OSA-friendly protocol. Our feasibility criteria included (1) participants successfully managing the technique at home; (2) participants completing daily practice sessions and recording data logs; and (3) capturing performance plateaus to determine an optimal length of the intervention. Methods: Five sedentary OSA patients participated in this feasibility study (three men, mean age = 61.6 years, SD = 10.2). Using a digital POWERbreathe K4 or K5 device, participants performed 30 daily inhalations against a resistance set at a percentage of maximum, recalculated weekly. Participants were willing to perform one but not two daily practice sessions. Intervention parameters from common IMT protocols were adapted according to ability and subjective feedback. Some were unable to perform the typically used 75% of maximum inspiratory resistance so we lowered the target to 65%. The technique required some practice; therefore, we introduced a practice week with a 50% target. After an initial 8 weeks, the intervention was open-ended and training continued until all participants demonstrated at least one plateau of inspiratory strength (2 weeks without strength gain). Weekly email and phone reminders ensured that participants completed all daily sessions and logged data in their online surveys. Weekly measures of inspiratory resistance, strength, volume, and flow were recorded. Results: Participants successfully completed the practice and subsequent 65% IMT resistance targets daily for 13 weeks. Inspiratory strength gains showed plateaus in all subjects by the end of 10 weeks of training, suggesting 12 weeks plus practice would be sufficient to achieve and capture maximum gains. Participants reported no adverse effects. Conclusion: We developed and tested a 13-week IMT protocol in a small group of sedentary, untreated OSA patients. Relative to other IMT protocols, we successfully implemented reduced performance requirements, a practice week, and an extended timeframe. This feasibility study provides the basis for a protocol for clinical trials on IMT in OSA.

Purpose

Cancer-related fatigue (CRF) is a common symptom experienced by cancer survivors. Persistent fatigue can last years after cancer treatment. CRF's origin is unknown, and there are no validated treatments. Cultural constructs (definitions, meaning, and explanations) may vary the presentation and treatment choices related to fatigue. Identifying and categorizing CRF terms and experiences among racial, ethnic, and non-English speaking groups may provide a fuller understanding of CRF to guide tailoring of interventions. We report on the cultural constructs of CRF as reported by American Indian cancer survivors.

Methods

A study of Southwest American Indians collected qualitative data on cancer survivors' experiences of fatigue. Focus groups (n = 132) at urban clinics and rural reservation sites in the Southwest collected qualitative data on cancer survivor experiences with fatigue. The sessions were audiotaped and transcribed verbatim. During analysis, common themes were coded and formed into categories following Grounded Theory analytical procedures. Relationships between categories were examined.

Results

CRF was described by survivors as an entity that comes into the brain, "drains life" from the body, and creates long-lasting suffering, pain, and stigma. We review the cultural constructs of fatigue and CRF's relationship to "being out of balance."

Conclusions

There is a need for culturally appropriate education concerning fatigue, techniques for reducing fatigue, and support for American Indian cancer survivors and other vulnerable populations.