Validity of a novel respiratory rate monitor comprising stretchable strain sensors during a 6-min walking test in patients with chronic pulmonary obstructive disease.

BACKGROUND: Breathing frequency is rarely measured during a field walking test since the current monitoring system using a face mask is cumbersome for older adults. For effective clinical application, we aimed to validate the new respiratory monitor using wearable strain sensors during a 6-min walk test (6MWT) in young adults and patients with chronic obstructive pulmonary disease (COPD). METHODS: The study included young adults and patients with stable COPD voluntarily recruited from three hospitals. Breathing frequency during 6MWT were measured by the strain sensor and a nasal capnometer. Total breathing frequencies were measured by the capnometer. The Bland-Altman method was used to estimate the mean limit of agreement for breathing frequency. RESULTS: A total of 23 young adults (age = 23.1 ± 3.7, mean ± SD) and 50 patients with COPD (age = 75.2 ± 7.2, %FEV1 = 59.1 ± 19.7) were analyzed. During the entire test period, the total breathing frequencies were measured based on an average of 252 ± 46 breaths, and the total breathing frequency was higher in patients with COPD than in young adults (mean difference = -3.349, p < 0.0013). The mean difference in breathing frequency between the strain sensors and capnometer was -0.28 (95%CI: 0.75 to 0.20), and the limit of agreement ranged from -4.1 to 3.6. The CI of the limit of agreement included the limit of equivalence (4 counts/min). CONCLUSIONS: The novel respiratory monitor with wearable sensors achieved the target accuracy in both young adults and patients with COPD in the 6MWT.

Reliability and Validity of the Japanese Version of the Barthel Index Dyspnea Among Patients with Respiratory Diseases.

Purpose: Japan has only a few respiratory disease-specific activity of daily living scales that are accepted outside of Japan, and they are not widely used. The Barthel Index dyspnea (BI-d), an improved version of the Barthel Index (BI), may be popular in Japan. The purpose of this study was to develop the Japanese version of BI-d (J-BI-d) and investigate its reliability and validity. Patients and Methods: The J-BI-d was developed using the basic guidelines for scale translation. The study included patients with chronic respiratory disease, receiving outpatient care at two centers between January 2019 and February 2020. Scores on the J-BI-d, modified Medical Research Council scale (mMRC scale), BI, respiratory function tests, and 6-minute walk distance (6MWD) test were measured. To verify the test-retest reliability, the J-BI-d was re-administered, and the intraclass correlation coefficient (ICC) was obtained. Internal consistency was verified by Cronbach's alpha reliability coefficient, and criterion-related validity was verified through a correlation analysis of the J-BI-d with mMRC scale and 6MWD test. Divergent validity was verified through correlation analysis between the J-BI-d and BI. Results: Data for 57 participants (mean age 74.4 ± 8.3 years) were analyzed, and reliability testing was performed with 42 of them. The mean time to retest was 8.1 ± 3.0 days, and the ICC (2, 1) was 0.76 (95% CI: 0.62-0.85), indicating high reliability. Cronbach's alpha reliability coefficient was 0.81, indicating high internal consistency. Correlation coefficients of the J-BI-d with 6MWD test (r = -0.46, p < 0.01) and mMRC scale (ρ = 0.76, p < 0.01) indicated high criterion-related validity. The J-BI-d and BI had a weak negative correlation (r = -0.29, p < 0.05), indicating high divergent validity. Conclusion: The results of this study demonstrate high reliability and appropriate validity of the J-BI-d in patients with chronic respiratory disease.

Measurement of laryngeal elevation time using a flexible surface stretch sensor.

BACKGROUND: Dysphagia is a growing health problem in aging societies. An observational cohort study targeting community-dwelling populations revealed that 16% of elderly subjects present with dysphagia. There is a need in elderly communities for systematic dysphagia assessment. OBJECTIVE: This study aimed to verify whether laryngeal elevation in the pharyngeal phase could be measured from the body surface using thin and flexible stretch sensors. METHODS: Thirty-two elderly subjects (17 males, 15 females; mean age ± SD: 89.2 ± 6.2 years) with suspected dysphagia underwent a swallowing contrast examination in which seven stretch sensors were attached to the front of the neck. The elongation of the sensors was measured and compared to the laryngeal elevation time values obtained using videofluorography. The sensor signal detected the laryngeal elevation start time, conclusion of the descent of the larynx, and the laryngeal elevation time. The respective laryngeal elevation times obtained using videofluorography and using the sensor were compared using the Bland-Altman method. RESULTS: The laryngeal elevation time was 1.34 ± 0.46 s with the stretch sensor and 1.49 ± 0.56 s with videofluorography. There was a significant positive correlation between the duration obtained by both methods (r = .69, P < .0001). A negative additional significant bias of -0.15 s (95% confidence interval -0.30 to -0.03, P = .046) was noted in the laryngeal elevation time from the videofluorography measurement. CONCLUSION: Laryngeal elevation time can be measured non-invasively from the neck surface using stretch sensors.

Pulmonary collectins protect macrophages against pore-forming activity of Legionella pneumophila and suppress its intracellular growth.

Pulmonary collectins, surfactant proteins A (SP-A) and D (SP-D), play important roles in innate immunity of the lung. Legionella pneumophila is a bacterial respiratory pathogen that can replicate within macrophages and causes opportunistic infections. L. pneumophila possesses cytolytic activity, resulting from insertion of pores in the macrophage membrane upon contact. We examined whether pulmonary collectins play protective roles against L. pneumophila infection. SP-A and SP-D bound to L. pneumophila and its lipopolysaccharide (LPS) and inhibited the bacterial growth in a Ca(2+)-dependent manner. The addition of LPS in the culture blocked the inhibitory effects on L. pneumophila growth by the collectins, indicating the importance of LPS-collectin interaction. When differentiated THP-1 cells were infected with L. pneumophila in the presence of SP-A and SP-D, the number of permeable cells was significantly decreased, indicating that pulmonary collectins inhibit pore-forming activity of L. pneumophila. The number of live bacteria within the macrophages on days 1-4 after infection was significantly decreased when infection was performed in the presence of pulmonary collectins. The phagocytosis experiments with the pH-sensitive dye-labeled bacteria revealed that pulmonary collectins promoted bacterial localization to an acidic compartment. In addition, SP-A and SP-D significantly increased the number of L. pneumophila co-localized with LAMP-1. These results indicate that pulmonary collectins protect macrophages against contact-dependent cytolytic activity of L. pneumophila and suppress intracellular growth of the phagocytosed bacteria. The promotion of lysosomal fusion with Legionella-containing phagosomes constitutes a likely mechanism of L. pneumophila growth suppression by the collectins.

Pulmonary surfactant protein D binds MD-2 through the carbohydrate recognition domain.

Pulmonary surfactant protein D (SP-D) is a member of the collectin family and plays crucial roles in the innate immunity of the lung. We have previously shown that surfactant protein A (SP-A), a homologous collectin, interacts with MD-2 and alters lipopolysaccharide signaling. In this study, we examined and characterized the binding of SP-D to MD-2 using a soluble form of recombinant MD-2 (sMD-2). SP-D bound in a concentration- and Ca(2+)-dependent manner to sMD-2 coated onto microtiter wells. Excess mannose abolished the binding of SP-D to sMD-2. In solution, SP-D cosedimented with sMD-2 in the presence of Ca(2+). The direct binding of SP-D to sMD-2 was confirmed by BIAcore analysis. Anti-SP-D monoclonal antibody that recognizes the carbohydrate recognition domain (CRD) of SP-D significantly inhibited the binding of SP-D to sMD-2, indicating the involvement of the CRD for the binding to sMD-2. Ligand blot analysis revealed that SP-D bound to N-glycopeptidase F-treated sMD-2. In addition, the biotinylated SP-D pulled down the mutant sMD-2 with Asn(26) --> Ala and Asn(114) --> Ala substitutions, which lacks the consensus for N-glycosylation. Furthermore, the sMD-2 mutant cosedimented SP-D. These results demonstrate that SP-D directly interacts with MD-2 through the CRD.

Pulmonary surfactant protein D inhibits lipopolysaccharide (LPS)-induced inflammatory cell responses by altering LPS binding to its receptors.

Pulmonary surfactant protein D (SP-D) is a member of the collectin family that plays an important role in regulating innate immunity of the lung. We examined the mechanisms by which SP-D modulates lipopolysaccharide (LPS)-elicited inflammatory cell responses. SP-D bound to a complex of recombinant soluble forms of Toll-like receptor 4 (TLR4) and MD-2 with high affinity and down-regulated tumor necrosis factor-alpha secretion and NF-kappaB activation elicited by rough and smooth LPS, in alveolar macrophages and TLR4/MD-2-transfected HEK293 cells. Cell surface binding of both serotypes of LPS to TLR4/MD-2-expressing cells was attenuated by SP-D. In addition, SP-D significantly reduced MD-2 binding to both serotypes of LPS. A chimera containing the N-terminal region and the collagenous domain of surfactant protein A, and the coiled-coil neck and lectin domains of SP-D, was a weak inhibitor of LPS-induced cell responses and MD-2 binding to LPS, compared with native SP-D. The collagenase-resistant fragment consisting of the neck plus the carbohydrate recognition domain of SP-D also was a very weak inhibitor of LPS activation. This study demonstrates that SP-D down-regulates LPS-elicited inflammatory responses by altering LPS binding to its receptors and reveals the importance of the correct oligomeric structure of the protein in this process.

Peripheral primitive neuroectodermal tumor of the chest wall of a 69-year-old man.

We report a case of peripheral primitive neuroectodermal tumor (pPNET), which belongs to the pPNET/Ewing's sarcoma family, arising in the chest wall of a 69-year-old man. He had high levels of serum neuron-specific enolase and pro-gastrin-releasing peptide, which are believed to be useful diagnostic blood markers for small cell lung carcinoma (SCLC). Microscopically, the tumor was composed of solid nests and sheets of monotous, primitive, small round cells with a few rosettes, making it difficult to distinguish from SCLC. Immunohistochemically, the tumor cells showed intense cell membranous immunoreactivity for MIC2 protein (CD99). EWS/FLI-1 chimeric mRNA that originated from the characteristic t(11;22)(q24;q12) chromosomal translocation was detected by RT-PCR and nucleotide sequence analysis. These results confirmed the diagnostic validity of the present tumor being a pPNET, thus raising the possibility that in the past, pPNETs which have arisen in the chest have been mistakenly diagnosed as SCLC.