The Phrenic Component of Acute Schizophrenia – A Name and Its Physiological Reality

Decreased heart rate variability (HRV) was shown for unmedicated patients with schizophrenia and their first-degree relatives, implying genetic associations. This is known to be an important risk factor for increased cardiac mortality in other diseases. The interaction of cardio-respiratory function and respiratory physiology has never been investigated in the disease although it might be closely related to the pattern of autonomic dysfunction. We hypothesized that increased breathing rates and reduced cardio-respiratory coupling in patients with acute schizophrenia would be associated with low vagal function. We assessed variability of breathing rates and depth, HRV and cardio-respiratory coupling in patients, their first-degree relatives and controls at rest. Control subjects were investigated a second time by means of a stress task to identify stress-related changes of cardio-respiratory function. A total of 73 subjects were investigated, consisting of 23 unmedicated patients, 20 healthy, first-degree relatives and 30 control subjects matched for age, gender, smoking and physical fitness. The LifeShirt®, a multi-function ambulatory device, was used for data recording (30 minutes). Patients breathe significantly faster (p<.001) and shallower (p<.001) than controls most pronouncedly during exhalation. Patients' breathing is characterized by a significantly increased amount of middle- (p<.001), high- (p<.001), and very high frequency fluctuations (p<.001). These measures correlated positively with positive symptoms as assessed by the PANSS scale (e.g., middle frequency: r = 521; p<.01). Cardio-respiratory coupling was reduced in patients only, while HRV was decreased in patients and healthy relatives in comparison to controls. Respiratory alterations might reflect arousal in acutely ill patients, which is supported by comparable physiological changes in healthy subjects during stress. Future research needs to further investigate these findings with respect to their physiological consequences for patients. These results are invaluable for researchers studying changes of biological signals prone to the influence of breathing rate and rhythm (e.g., functional imaging)

Cardiovascular response to physical exercise in adult patients after atrial correction for transposition of the great arteries assessed with magnetic resonance imaging

Objective: To assess with magnetic resonance imaging (MRI) cardiovascular function in response to exercise in patients after atrial correction of transposition of the great arteries (TGA). Methods: Cardiac function at rest and during submaximal exercise was assessed with MRI in 27 patients with TGA (mean (SD) age 26 (5) years) late (23 (2) years) after atrial correction and in 14 control participants (25 (5) years old). Results: At rest, only right ventricular ejection fraction was significantly lower in patients than in controls (56 (7)% v 65 (7)%, p < 0.05). In response to exercise, increases in right ventricular end diastolic (155 (55) ml to 163 (57) ml, p < 0.05) and right ventricular end systolic volumes (70 (34) ml to 75 (36) ml, p < 0.05) were observed in patients. Furthermore, right and left ventricular stroke volumes and ejection fraction did not increase significantly in patients. Changes in right ventricular ejection fraction with exercise correlated with diminished exercise capacity (r  =  0.43, p < 0.05). Conclusions: In patients with atrially corrected TGA, MRI showed an abnormal response to exercise of both systemic right and left ventricles. Exercise MRI provides a tool for close monitoring of cardiovascular function in these patients, who are at risk for late death

The legend of the buffalo chest

Background The “buffalo chest” is a condition in which a simultaneous bilateral pneumothorax occurs due to a communication of both pleural cavities caused by an iatrogenic or idiopathic fenestration of the mediastinum. This rare condition is known by many clinicians because of a particular anecdote which stated that Native Americans could kill a North American bison with a single arrow in the chest by creating a simultaneous bilateral pneumothorax, due to the animal’s peculiar anatomy in which there is one contiguous pleural space due to an incomplete mediastinum. Research Question What evidence is there for the existence of buffalo chest? Study Design and Methods The term “buffalo chest” and its anecdote were first mentioned in a ‘‘personal communication’’ by a veterinarian in the Annals of Surgery in 1984. A mixed method research was performed on buffalo chest and its etiology. A total of 47 cases of buffalo chest were identified in humans. Results This study found that all authors were referring to the article from 1984 or to each other. Evidence was found for interpleural communications in other mammal species, but no literature on the anatomy of the mediastinum of the bison was found. The main reason for this research was fact-checking the origin of the anecdote and search for evidence for the existence of buffalo chest. Autopsies were performed on eight bison, and four indeed were found to have had interpleural communications. Interpretation We hypothesize that humans can also have interpleural fenestrations, which can be diagnosed when a pneumothorax occurs

Expression of smooth muscle and extracellular matrix proteins in relation to airway function in asthma

BACKGROUND: Smooth muscle content is increased within the airway wall in patients with asthma and is likely to play a role in airway hyperresponsiveness. However, smooth muscle cells express several contractile and structural proteins, and each of these proteins may influence airway function distinctly. OBJECTIVE: We examined the expression of contractile and structural proteins of smooth muscle cells, as well as extracellular matrix proteins, in bronchial biopsies of patients with asthma, and related these to lung function, airway hyperresponsiveness, and responses to deep inspiration. METHODS: Thirteen patients with asthma (mild persistent, atopic, nonsmoking) participated in this cross-sectional study. FEV(1)% predicted, PC(20) methacholine, and resistance of the respiratory system by the forced oscillation technique during tidal breathing and deep breath were measured. Within 1 week, a bronchoscopy was performed to obtain 6 bronchial biopsies that were immunohistochemically stained for alpha-SM-actin, desmin, myosin light chain kinase (MLCK), myosin, calponin, vimentin, elastin, type III collagen, and fibronectin. The level of expression was determined by automated densitometry. RESULTS: PC(20) methacholine was inversely related to the expression of alpha-smooth muscle actin (r = -0.62), desmin (r = -0.56), and elastin (r = -0.78). In addition, FEV(1)% predicted was positively related and deep inspiration-induced bronchodilation inversely related to desmin (r = -0.60), MLCK (r = -0.60), and calponin (r = -0.54) expression. CONCLUSION: Airway hyperresponsiveness, FEV(1)% predicted, and airway responses to deep inspiration are associated with selective expression of airway smooth muscle proteins and components of the extracellular matri

From Genetics to Clinical Implications: A Study of 675 Dutch Osteogenesis Imperfecta Patients

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder that causes bone fragility due to pathogenic variants in genes responsible for the synthesis of type I collagen. Efforts to classify the high clinical variability in OI led to the Sillence classification. However, this classification only partially takes into account extraskeletal manifestations and the high genetic variability. Little is known about the relation between genetic variants and phenotype as of yet. The aim of the study was to create a clinically relevant genetic stratification of a cohort of 675 Dutch OI patients based on their pathogenic variant types and to provide an overview of their respective medical care demands. The clinical records of 675 OI patients were extracted from the Amsterdam UMC Genome Database and matched with the records from Statistics Netherlands (CBS). The patients were categorized based on their harbored pathogenic variant. The information on hospital admissions, outpatient clinic visits, medication, and diagnosis-treatment combinations (DTCs) was compared between the variant groups. OI patients in the Netherlands appear to have a higher number of DTCs, outpatient clinic visits, and hospital admissions when compared to the general Dutch population. Furthermore, medication usage seems higher in the OI cohort in comparison to the general population. The patients with a COL1A1 or COL1A2 dominant negative missense non-glycine substitution appear to have a lower health care need compared to the other groups, and even lower than patients with COL1A1 or COL1A2 haploinsufficiency. It would be useful to include the variant type in addition to the Sillence classification when categorizing a patient’s phenotype

Key4OI Recommendations for Lung Function Guidance in Osteogenesis Imperfecta Based on an Internationally Performed Comprehensive ICHOM Procedure

INTRODUCTION: Pulmonary involvement in Osteogenesis Imperfecta (OI) can be severe but may be overlooked in milder cases. The Care4BrittleBones Foundation initiated this project to develop a set of global outcome measures focusing on respiratory-related issues in patients with OI. The objective was to reach an international consensus for a standardized set of outcomes and associated measuring instruments for the pulmonary care of individuals with OI. Based on the initial tests and questionnaires, we suggest parameters for when pulmonologists should seek guidance from the growing literature on OI pulmonary care and/or recognized experts in the field. International Consortium for Health Outcomes Measurement (ICHOM) METHODS: The project team consisted of a multidisciplinary mix of 12 people from 6 countries, including an OI patient representative and facilitated by the Care4BrittleBones Foundation director. The International Consortium for Health Outcomes Measurement (ICHOM) process was followed, which includes the Delphi method, used to collect the opinions of the expert team. Patient input was present in each meeting due to the inclusion of a patient representative. In addition, online focus groups were held. They consed of adults with OI from different countries and they determined which questions matter the most to the OI community worldwide. RESULTS: After 3 Delphi rounds, the expert team reached a consensus on the final set of measuring instruments, which included pulmonary function testing and patient self-reporting of symptoms related to breathing and sleep. Two questionnaires were decided upon: St. George\u27s Respiratory Questionnaire (shortened version) and four questions regarding sleep. Patients should be screened for a history of pneumonia. Advanced testing for select patients by a pulmonologist would include further pulmonary function tests and a chest x-ray. CONCLUSIONS: A standardized set of outcome measures related to pulmonary care of individuals with OI was determined based on what is important to both experts and patients. This included patient-reported outcome measures and basic pulmonary function testing. Using these outcome measures, it can be determined which patients are at high risk for pulmonary complications