Cigarette smoke-induced emphysema: A role for the B cell?

RATIONALE: Little is known about what drives the inflammatory reaction in the development of chronic obstructive lung disease. B cells have been found. OBJECTIVE: To study the involvement of B cells in the development of emphysema. METHODS: The presence of B-cell follicles and their interaction with other cells were investigated in lungs of patients with chronic obstructive pulmonary disease and of smoking mice. B cells were isolated from lymphoid follicles by laser microdissection and analyzed for the presence of immunoglobulin rearrangements and somatic mutations. MAIN RESULTS: Lymphoid follicles consisting of B cells and follicular dendritic cells with adjacent T cells were demonstrated both in the parenchyma and in bronchial walls of patients with emphysema. A clonal process was observed in all follicles and the presence of ongoing somatic mutations was observed in 75% of the follicles, indicating oligoclonal, antigen-specific proliferation. Similar lymphoid follicles were detected in mice that had developed pulmonary inflammation and progressive alveolar airspace enlargement after smoking. The increase in the number of B-cell follicles was progressive with time and correlated with the increase in mean linear intercept. Specific bacterial or viral nucleic acids could not be detected. CONCLUSIONS: B-cell follicles with an oligoclonal, antigen-specific reaction were found in men and mice with emphysema. In mice, the development was progressive with time and correlated with the increase in airspace enlargement. We hypothesize that these B cells contribute to the inflammatory process and/or the development and perpetuation of emphysema by producing antibodies against either tobacco smoke residues or extracellular matrix components.     

Long-Term Effects of Orthoses Use on the Changes of Foot and Ankle Joint Motions of Children With Spastic Cerebral Palsy

Background

Orthoses commonly are prescribed to children with cerebral palsy (CP) to provide foot correction and to improve ambulatory function. Immediate effects of ankle foot orthosis (AFOs) have been investigated, but long-term kinematic effects are lacking clinical evidence.

Physician and Patient Attitudes Toward Obesity

Several studies have found that health care professionals tend to hold negative attitudes regarding obesity. The degree to which patients perceive these attitudes, however, remains unclear. This study examined physicians’ and their obese patients’ attitudes toward obesity. In addition, the physicians’ attitudes were compared with their obese patients’ perceptions of their physicians’ attitudes. Though both physicians and their obese patients reported ambivalent overall attitudes regarding obesity, the physicians reported less negative attitudes than what their patients perceived. The implications of the findings are discussed, and suggestions for future research are offered.     

Recent advances in chronic obstructive pulmonary disease pathogenesis: from disease mechanisms to precision medicine

Chronic obstructive pulmonary disease (COPD) is a devastating lung disease with a high personal and societal burden. Exposure to toxic particles and gases, including cigarette smoke, is the main risk factor for COPD. Together with smoking cessation, current treatment strategies of COPD aim to improve symptoms and prevent exacerbations, but there is no disease-modifying treatment. The biggest drawback of today's COPD treatment regimen is the ‘one size fits all’ pharmacological intervention, mainly based on disease severity and symptoms and not the individual's disease pathology. To halt the worrying increase in the burden of COPD, disease management needs to be advanced with a focus on personalized treatment. The main pathological feature of COPD includes a chronic and abnormal inflammatory response within the lungs, which results in airway and alveolar changes in the lung as reflected by (small) airways disease and emphysema. Here we discuss recent developments related to the abnormal inflammatory response, ECM and age-related changes, structural changes in the small airways and the role of sex-related differences, which are all relevant to explain the individual differences in the disease pathology of COPD and improve disease endotyping. Furthermore, we will discuss the most recent developments of new treatment strategies using biologicals to target specific pathological features or disease endotypes of COPD. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Foot and ankle joint movements inside orthoses for children with spastic CP

We compared the ankle joint and foot segment kinematics of pediatric cerebral palsy (CP) participants walking with and without orthoses. A six segment foot model (6SF) was used to track foot motion. Holes were cut in the study orthoses so that electromagnetic markers could be directly placed on the skin. The Hinged Ankle Foot Orthoses (HAFO) allowed a significant increase in ankle dorsiflexion as compared to the barefoot condition during gait, but significantly constrained sagittal forefoot motion and forefoot sagittal range of motion (ROM) (p < 0.01), which may be detrimental. The Solid Ankle Foot Orthoses (SAFO) constrained forefoot ROM as compared to barefoot gait (p < 0.01). The 6SF model did not confirm that the SAFO can control excessive plantarflexion for those with severe plantarflexor spasticity. The supramalleolar orthosis (SMO) significantly (p < 0.01) constrained forefoot ROM as compared to barefoot gait at the beginning and end of the stance phase, which could be detrimental. The SMO had no effects observed in the coronal plane. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:531–536, 2014.     

Correspondence between neurophysiological and clinical measurements of chemotherapy‐induced peripheral neuropathy: secondary analysis of data from the CI‐PeriNomS study

Chemotherapy‐induced peripheral neuropathy (CIPN) lacks standardized clinical measurement. The objective of the current secondary analysis was to examine data from the CIPN Outcomes Standardization (CI‐PeriNomS) study for associations between clinical examinations and neurophysiological abnormalities. Logistic regression estimated the strength of associations of vibration, pin, and monofilament examinations with lower limb sensory and motor amplitudes. Examinations were classified as normal (0), moderately abnormal (1), or severely abnormal (2). Among 218 participants, those with class 1 upper extremity (UE) and classes 1 or 2 lower extremity (LE) monofilament abnormality were 2.79 (95% confidence interval [CI]: 1.28–6.07), 3.49 (95%CI: 1.61–7.55), and 4.42 (95%CI: 1.35–14.46) times more likely to have abnormal sural nerve amplitudes, respectively, compared to individuals with normal examinations. Likewise, those with class 2 UE and classes 1 or 2 LE vibration abnormality were 8.65 (95%CI: 1.81–41.42), 2.54 (95%CI: 1.19–5.41), and 7.47 (95%CI: 2.49–22.40) times more likely to have abnormal sural nerve amplitudes, respectively, compared to participants with normal examinations. Abnormalities in vibration and monofilament examinations are associated with abnormal sural nerve amplitudes and are useful in identifying CIPN.