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Introduction Gulf War Illness (GWI) affects 1 in 7 returned Persian Gulf War veterans. Quality-of-life impact is large; there is no cure. Chronic sinus symptoms and fatigue are common. Nasal irrigation with saline (NI-S) or xylitol (NI-X) improve sinus symptoms and fatigue in the general population. This trial will assess the effect of S-NI and X-NI on sinus and fatigue symptoms, economic outcomes and pro-inflammatory milieu among participants with GWI. Methods 75 participants (age 35 to 65 years, 25 in each of three arms) with GWI will be recruited from the Veteran’s Administration and the community. They will use routine care for sinus symptoms and fatigue and be randomized to continued usual care alone or additional therapy with NI-S or NI-X. Participants will be able to adjust specific elements of the NI procedure. The primary outcome (Sinonasal Outcome Test, SNOT-20) and other self-reported assessments will occur at baseline, 8 and 26 weeks; lab assessment of pro-inflammatory cellular and cytokine profiles will occur at baseline and 26 weeks. Other outcomes will include fatigue-specific and overall health-related quality of life, pro-inflammatory cellular and cytokine profiles, cost-effectiveness and participant satisfaction. Results Baseline demographic and clinical data from the first 10 participants show effective participant recruitment, enrollment, randomization, retention and data collection. Conclusion Early study conduct suggests that our participant-oriented approach will yield high rates of participant adherence and data capture, facilitating robust analysis. Results of this study will clarify the value of NI for chronic sinus symptoms and fatigue among patients with GWI. Clinical trial registration Clinical Trials.gov identifier NCT01700725.

Diagnosing the cause of hypoxemia and dyspnea can be complicated in complex patients with multiple co-morbidities. This Case Study in Physiology describes an obese man admitted to the hospital for relapse of acute lymphoblastic leukemia, who experienced progressive hypoxemia, shortness of breath, and dyspnea on exertion during his hospitalization. After initial empirical treatment with diuresis and antibiotics failed to improve his symptoms, we applied a novel, recently described physiological method to estimate the arterial partial pressure of oxygen from the peripheral saturation measurement, and calculate the alveolar-arterial oxygen difference to discern the source of his hypoxemia and dyspnea. Using basic physiological principles, we describe how hypoventilation, anemia, and the use of a beta-blocker and furosemide, collaborated to create a "perfect storm" in this patient that impaired oxygen delivery and limited utilization. This case illustrates the application of innovative physiology methodology in medicine and provides strong rationale for continuing to integrate physiology education in medical education.

Early and accurate diagnosis of emphysema is vital to reducing the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD). Visual assessments of chest computed tomography (CT) scans are routinely employed in the radiologic diagnosis of emphysema. While the advent of quantitative CT (QCT) has complemented visual CT, a phenomenon of discordant visual and QCT findings for the presence or absence of emphysema has been described. The purposes of this study are: to examine the association between visual and QCT assessments within a large cohort of subjects; and to identify variables that may explain discordant visual and QCT findings. METHODS: We included volumetric inspiratory CT scans of 1221 subjects enrolled in Phase 1 of the COPDGene study conducted at the University of Iowa study center. Subjects comprised of normal non-smokers, smokers with Preserved Ratio Impaired Spirometry, and smokers with all stages of COPD. CT scans were quantitatively scored and visually interpreted by the COPDGene Imaging Center and the study center's radiologists. Individual-level visual assessments were compared with QCT measurements. Interobserver agreement was calculated using the kappa statistic. We assessed variables associated with discordant results using multivariable logistic regression analysis. RESULTS: There was a fair agreement for the presence or absence of emphysema between the study center's radiologists and QCT [61% concordance, kappa 0.22 (0.17-0.28)]. Similar comparisons showed a slight agreement between the COPDGene Imaging Center and QCT [56% concordance, kappa 0.16 (0.11-0.21)], and a moderate agreement between both sets of visual assessments [80% concordance, kappa 0.60 (0.54-0.65)]. Smoking pack-years, airway wall area percent in subsegmental bronchi, and female sex were significantly associated with QCT-detectable but visually-negative emphysema. CONCLUSIONS: The slight-to-fair agreement between visual and quantitative CT assessment of emphysema highlights the need to utilize both modalities for a comprehensive radiologic evaluation. Discordant results may be attributable to one or more factors that warrant further exploration in larger studies. CLINICAL IMPLICATIONS: Visual and quantitative CT analyses are complementary tools in the radiologic identification of emphysema. Awareness of the factors potentially affecting discordant results is necessary for making a clinical judgment about the presence or absence of emphysema.

The flow–volume loop (FVL) analysis is typically helpful in establishing the diagnosis of airway obstruction caused by endobronchial lesions. In this report, we describe a patient with emphysema and tobacco abuse who presented with chronic dry cough and severe chronic obstructive pulmonary disease (COPD) refractory to standard therapy. The initial FVL showed a relatively normal forced expiratory peak flow shape followed by a smooth flattening of the expiratory curve on spirometry, a pattern consistent with distal airway obstruction as seen in severe asthma or COPD. The patient was later found to have a large endotracheal mass. This atypical presentation, along with the unusual FVL, led to a significant delay in the diagnosis of the tracheal mass. A high level of suspicion is needed to diagnose variable intrathoracic airway obstruction in patients presenting with severe asthma or COPD who fail to improve with standard therapy.

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Chronic obstructive pulmonary disease (COPD) is a common lung disease characterized by limited expiratory airflow due to lung destruction or airway obstruction. Chest wall strapping (CWS) is a potential therapy technique that restricts the upper abdomen, inducing breathing at lower lung volumes and opening small airways. Although the respiratory impacts of CWS have been examined, the relationship between CWS and the cardiovascular system, which is closely tied to ventilation, has not been well‐established. Additionally, COPD patients have reduced autonomic nervous system activity, which may be reflected in cardiorespiratory coupling. Cardiorespiratory coupling causes increased heart rate during inhalation to accommodate for increased blood return. The strength of this relationship was evaluated during CWS in five COPD and six control patients by analyzing heart rate changes during ventilation cycles. Heart rate and ventilatory data were collected during baseline, CWS, and post‐CWS removal periods. Average heart rate during each inhalation and exhalation was plotted against tidal volume, with the slope of the linear regression representing the strength of the cardiorespiratory coupling relationship (BPM/L). Multi‐factor ANOVA statistics showed a significantly diminished strength in COPD patients compared to control (p < 0.001). There was no significant change in either group post‐CWS, suggesting that the same‐sized breaths will cause the heart to respond similarly regardless of the total lung capacity. A potential consequence of diminished cardiorespiratory coupling in COPD patients is strain on the right side of the heart, which then has to pump larger stroke volumes. Blunted cardiorespiratory coupling is not further impaired by CWS.

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