Direct current stimulation as a non-invasive therapeutic alternative for treating autonomic or non-autonomic neurological disorders affecting breathing.

Direct current stimulation (DCS) is a non-invasive approach to stimulate the nervous system that is now considered a powerful tool for treating neurological diseases such as those affecting cognitive or locomotor functions. DCS, as applied clinically today, is an approach built on early uses in antiquity and knowledge gained over time. Its current use makes use of specific devices and takes into account knowledge of the mechanisms by which this approach modulates functioning of the nervous system at the cellular level. Over the last 20 years, although there are few studies, it has been shown that DCS can also modulate the breathing autonomic function. In this narrative review, after briefly providing the historical perspective and describing the principles and the main cellular and molecular effects, we summarize the currently available data regarding the modulation of ventilation, and propose that DCS could be used to treat autonomic or non-autonomic neurological disorders affecting breathing.

Quantification of breathing irregularity for the diagnosis of dysfunctional breathing using proportional tidal volume variation: a cross-sectional, retrospective real-world study.

OBJECTIVES: To develop a statistical approach that provides a quantitative index measuring the magnitude of the irregularity of the breathing response to exercise for the diagnosis of dysfunctional breathing. DESIGN: Cross-sectional, retrospective, real-world study. SETTING: Single-centre study. PARTICIPANTS: A population of 209 patients investigated with cardiopulmonary exercise testing in our institution for unexplained or disproportionate exertional dyspnoea between January and July 2022. PRIMARY AND SECONDARY OUTCOME MEASURES: A novel statistical approach providing a quantitative index-proportional tidal volume variation (PTVV)-was developed to measure the magnitude of the irregularity of the breathing response to exercise. RESULTS: PTVV provided a reliable statistical readout for the objective assessment of DB with a prediction accuracy of 78% (95% CI: 72 to 83%). The prevalence of DB in the investigated population was high with more than half of the patients affected by moderate-to-severe DB. CONCLUSIONS: PTVV can easily be implemented in the clinical routine. Our study suggests a possible further simplification for the diagnosis of DB with two objective criteria including PTVV and one single criterion for hyperventilation.

A Systematic Literature Review of the Natural History of Respiratory, Swallowing, Feeding, and Speech Functions in Spinal Muscular Atrophy (SMA).

Background: Respiratory and bulbar dysfunctions (including swallowing, feeding, and speech functions) are key symptoms of spinal muscular atrophy (SMA), especially in its most severe forms. Demonstrating the long-term efficacy of disease-modifying therapies (DMTs) necessitates an understanding of SMA natural history. Objective: This study summarizes published natural history data on respiratory, swallowing, feeding, and speech functions in patients with SMA not receiving DMTs. Methods: Electronic databases (Embase, MEDLINE, and Evidence-Based Medicine Reviews) were searched from database inception to June 27, 2022, for studies reporting data on respiratory and/or bulbar function outcomes in Types 1-3 SMA. Data were extracted into a predefined template and a descriptive summary of these data was provided. Results: Ninety-one publications were included: 43 reported data on respiratory, swallowing, feeding, and/or speech function outcomes. Data highlighted early loss of respiratory function for patients with Type 1 SMA, with ventilatory support typically required by 12 months of age. Patients with Type 2 or 3 SMA were at risk of losing respiratory function over time, with ventilatory support initiated between the first and fifth decades of life. Swallowing and feeding difficulties, including choking, chewing problems, and aspiration, were reported in patients across the SMA spectrum. Swallowing and feeding difficulties, and a need for non-oral nutritional support, were reported before 1 year of age in Type 1 SMA, and before 10 years of age in Type 2 SMA. Limited data relating to other bulbar functions were collated. Conclusions: Natural history data demonstrate that untreated patients with SMA experience respiratory and bulbar function deterioration, with a more rapid decline associated with greater disease severity. This study provides a comprehensive repository of natural history data on bulbar function in SMA, and it highlights that consistent assessment of outcomes in this area is necessary to benefit understanding and approval of new treatments.

Clinical correlates of respiratory disorders in patients with severe multiple sclerosis: A cross-sectional cohort.

BACKGROUND: Respiratory disorders remain incompletely described in multiple sclerosis (MS), even though they are a frequent cause of death. METHODS: The objective was to describe respiratory disorders in MS patients with Expanded Disability Status Score (EDSS) ⩾ 6.5. Diaphragm dysfunction was defined by at least two of the seven criteria: clinical signs, inspiratory recruitment of neck muscles during wakefulness, reduced upright vital capacity (VC) < 80%, upright-to-supine VC ⩾ 15% of upright VC, decrease in Maximal Inspiratory Pressure < 60%, phasic activation of inspiratory neck muscles during sleep, and opposition of thoracic and abdominal movements during sleep. Cough weakness was defined by a peak cough flow < 270 L/min and/or need for cough assist. Sleep apnea syndrome was defined by an apnea-hypopnea index ⩾ 15. RESULTS: Notably, 71 MS patients were included: median age 54 [48, 61] years; median disease duration 21.4 [16.0, 31.4] years. Of these, 52 patients had one or more respiratory disorders; diaphragm dysfunction was the most frequent (n = 34). Patients with diaphragm dysfunction and cough weakness were more disabled. The fatigue score and the cognitive evaluations did not differ between the groups. Five patients required non-invasive ventilation. CONCLUSION: Respiratory disorders are frequent in severe MS, mostly diaphragm dysfunction. Of interest, instrumental interventions are available to address these disorders.

Respiratory dysfunction in persistent somatic symptoms: A systematic review of observational studies.

OBJECTIVE: This systematic review aims to analyze the existing literature investigating respiratory functioning in people with Persistent Somatic Symptoms (PSS) compared to healthy controls, to identify patterns of respiratory disturbances by symptom or syndrome, and describe any respiratory outcomes consistent across diagnoses. METHODS: A systematic review following PRISMA guidelines was conducted. A comprehensive search was carried out across five databases (PubMed (NCBI), PsycArticles (Ovid), Web of Science (Core Collection), Embase, and Scopus) using two customised search strings for persistent somatic symptoms and objective respiratory parameters. Title/abstract screening and data extraction were carried out independently by two reviewers. The modified Newcastle-Ottawa Scale was used for quality assessment of the studies. Studies investigating baseline respiratory functioning in adult patients with PSS compared to healthy controls, using at least one objective respiratory were included. RESULTS: 18 studies met the inclusion criteria for the review, with a pooled sample size of n = 3245. Chronic pain conditions were found to be the most prevalent subset of diagnoses of interest, comprising six of the studies. 10 studies included measures of lung capacity, flow and/or volume, nine studies reported measures of ventilation, and four studies investigated respiratory muscle functioning. 13 of the included studies reported significant differences in at least one objective respiratory measure between groups (at rest). Scores on self-reported measures of dysnpea and breathlessness were higher in patients compared to healthy controls, while objective respiratory outcomes were varied. CONCLUSION: The current systematic review is consistent with previous literature suggesting more pronounced experiences of breathlessness in patients with PSS, and significant disparities between reported dyspnea and objective respiratory outcomes. Research investigating the uncoupling between subjective and objective respiratory outcomes is needed to understand the mechanisms behind breathing disturbances in PSS.

Respiratory dysfunction in degenerative cervical myelopathy: A systematic review.

INTRODUCTION: Degenerative cervical myelopathy is a condition of symptomatic cervical spinal cord compression secondary to a range of degenerative spinal pathology. Respiratory symptoms such as shortness of breath are not uncommonly reported by people with DCM and respiratory dysfunction has been described in several DCM studies. The objective of this review was therefore to systematically synthesise the current evidence on the relationship between DCM and respiratory function. METHODS: The review was registered on PROSPERO and adhered to PRISMA guidelines. Ovid MEDLINE and Embase were searched from inception to 14th March 2023. DCM studies reporting on any measure or outcome relating to respiratory function or disease were eligible. Reference lists of included studies and relevant reviews articles were hand searched. Title, abstract and full text screening, risk of bias and GRADE assessments were completed in duplicate. A quantitative synthesis is presented. RESULTS: Of 1991 studies identified by literature searching, 13 met inclusion criteria: 3 cohort studies, 5 case-control studies, 1 case series and 4 case studies. Forced vital capacity (FVC), peak expiratory flow rate (PEFR) and maximal voluntary ventilation (MVV) were reported to be lower in DCM patients than controls; there was inconsistency in comparisons of forced expiratory volume in 1 s (FEV1). There was conflicting evidence on whether surgical decompression was associated with improvements in respiratory parameters and on the relationship between level of spinal cord compression and respiratory dysfunction. CONCLUSION: DCM may be associated with respiratory dysfunction. However, consistency and quality of evidence is currently low. Further work should characterise respiratory dysfunction in DCM patients more rigorously and investigate putative mechanisms such as disruption to cervical nerve roots responsible for diaphragmatic innervation and damage to descending spinal projections from brainstem respiratory centres.

Recuperación laboral clínica y funcional a 3 meses del alta en pacientes hospitalizados por neumonía por SARS-CoV-2: relación con la terapia recibida / Clinical and functional recovery and return to work 3 months after discharge in patients hospitalized for SARS-CoV-2 pneumonia: relationship with the therapy received

Resumen Introducción: La presentación clínica de neumonía por COVID-19 ha sido bien documentada; sin embargo, sus repercusiones a largo plazo son aún motivo de investigación. Objetivo: Evaluar la recuperación laboral, clínica y funcional respiratoria, a 3 meses del egreso de pacientes hospitalizados por neumonía por SARS-CoV-2, en relación con la terapia ventilatoria recibida. Pacientes y Métodos: Se analizó una cohorte prospectiva de 116 pacientes con neumonía por COVID-19 del Hospital Naval Almirante Nef de Viña del Mar, con seguimiento clínico y funcional respiratorio 3 meses después de su alta. Resultados: Mediana del seguimiento: 100 días. Constitución de la cohorte: 75 hombres, mediana de edad 60 años, 50% obesos, 34,5% fumadores y 13,8% con comorbilidad respiratoria. 16% recibió rehabilitación. Se reportó disnea en 48,3% y fatigabilidad en 33,6%. Solo 54,8% retornó al trabajo. El 65,2% que utilizó oxigenoterapia (O2) volvió a trabajar comparado con 44% que utilizó cánula nasal de alto flujo (CNAF) y 33,3% con ventilación mecánica invasiva (VMI). Mayoritariamente el grupo de O2 volvió a la vida normal en comparación con CNAF y VMI (71,4 versus 17,5% y 11,1% respectivamente). La función pulmonar fue normal en 39 pacientes (33,6%). La serie que volvió a vida normal tuvo mayor porcentaje de DLCO y test de caminata de 6 minutos normales. En comparación con la serie O2, la serie CNAF tuvo mayor frecuencia de alteración de DLCO (OR = 5) seguido por la serie VMI (OR = 3,6). Conclusión: A 3 meses de seguimiento, se evidenció ausentismo laboral, persistencia de síntomas y alteración funcional respiratoria (DLCO), especialmente en quienes recibieron soporte ventilatorio adicional a oxigenoterapia.

Introduction: The clinical presentation of COVID-19 pneumonia has been well documented; however, its long-term repercussions are still a matter of investigation. Objective: to evaluate the occupational, clinical and functional respiratory recovery, 3 months after the discharge of patients hospitalized for SARS-CoV-2 pneumonia, in relation to the ventilatory therapy received. Patients and Methods: A prospective cohort of 116 patients with COVID-19 pneumonia from Hospital Naval Almirante Nef (Viña del Mar, Chile) was analyzed, with clinical and functional respiratory follow-up at 3 months after being discharged. Results: Median follow-up: 100 days. Composition of the cohort: 75 men, median age 60 years-old, 50% obese, 34.5% smokers and 13.8% with respiratory comorbidity. 16% received rehabilitation. Dyspnea was reported in 48.3% and fatigue in 33.6%. Only 54.8% returned to work. 65.2% who used oxygen therapy (O2) returned to work compared to 44% who used high-flow nasal cannula (HFNC) and 33.3% with invasive mechanical ventilation (IMV). Mostly the O2 group returned to normal life compared to HFNC and VMI (71.4 versus 17.5% and 11.1% respectively). Lung function was normal in 39 patients (33.6%). The series that returned to normal life had higher percentage of normal DLCO and six-minute walk test. Compared to the O2 series, the CNAF series had a higher frequency of DLCO alteration (OR = 5) followed by the VMI series (OR = 3.6). Conclusion: At 3 months of follow-up, absenteeism from work, persistence of symptoms and respiratory functional alteration (DLCO) were evident, especially in those who received ventilatory support in addition to oxygen therapy.

Experienced Respiratory Symptoms and the Impact on Daily Life from the Perspective of People with Parkinson's Disease: A Grounded Theory.

BACKGROUND: Abnormal respiratory function tests can be observed early in the course of Parkinson's disease (PD). A better understanding of the impact of respiratory dysfunction on daily life in PD is needed to prevent later occurring complications as a (aspiration) pneumonia. OBJECTIVE: To explain which respiratory symptoms people with PD or a form of atypical parkinsonism experience and how these symptoms impact on their daily lives. METHODS: This qualitative study used a grounded theory approach. A purposeful sample strategy was used to capture information-rich cases. Data were collected in semi-structured interviews with participants diagnosed with either PD (n = 11) or atypical parkinsonism (n = 3), all of whom had confirmed respiratory symptoms. Data were analyzed using grounded theory analysis by creating codes, categories, theoretical themes, and, ultimately, a conceptual model. RESULTS: Four respiratory profiles emerged, describing different types of respiratory dysfunction, with various positive and negative influencing factors. First, a loss of breathing automatism was experienced. Second, episodes of breathlessness or a rapid, shallow breathing pattern were triggered by either physical exertion, fatigue, or postural deformities. Third, stress and anxiety also triggered episodes of breathlessness. Fourth, a decreased cough strength and frequent coughing. Based on these findings, we constructed a conceptual model that visualizes the relations between these four types of respiratory dysfunction and their impact on daily life, with 'discomfort' and 'avoidance of social activities' as crucial elements. CONCLUSION: A tailored approach for each profile of respiratory dysfunction is recommended to improve respiratory dysfunction and to reduce its social impact in people with PD.

Respiratory disorders of Parkinson's disease.

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, mainly affecting people over 60 yr of age. Patients develop both classic symptoms (tremors, muscle rigidity, bradykinesia, and postural instability) and nonclassical symptoms (orthostatic hypotension, neuropsychiatric deficiency, sleep disturbances, and respiratory disorders). Thus, patients with PD can have a significantly impaired quality of life, especially when they do not have multimodality therapeutic follow-up. The respiratory alterations associated with this syndrome are the main cause of mortality in PD. They can be classified as peripheral when caused by disorders of the upper airways or muscles involved in breathing and as central when triggered by functional deficits of important neurons located in the brainstem involved in respiratory control. Currently, there is little research describing these disorders, and therefore, there is no well-established knowledge about the subject, making the treatment of patients with respiratory symptoms difficult. In this review, the history of the pathology and data about the respiratory changes in PD obtained thus far will be addressed.

Clinical efficacy of non-invasive ventilation combined with Chinese medicine for intestinal regulation in Chinese children with respiratory disorders.

Chinese medicine for intestinal regulation is an emerging method for pediatric respiratory disorders, which has better clinical value when combined with NIV (Non-invasive ventilation). This study aims to observe the clinical efficacy of NIV plus Chinese medicine for intestinal regulation in Chinese children with respiratory disorders. Thirty-nine patients admitted to Huaihua First People's Hospital, between March 2016 and July 2018 were enrolled, including 14 children with chronic hypercapnic respiratory failure, 19 with non-surgical OSAS, 5 with OB and 1 with central hypoventilation syndrome. After NIV, the blood gas carbon dioxide retention and labored breathing were improved, respiratory rate and heart rate were decreased and the feeding condition of some children improved. After NIV treatment, clinical symptoms of children with OSAS were significantly ameliorated. In polysomnography monitoring, the AHI, OAI and SpO2 were significantly enhanced following NIV. In addition, patients with OB and central hypoventilation had different degrees of improvement of their symptoms. NIV plus Chinese medicine for intestinal regulation alleviate the clinical symptoms and enhances the quality of life of children with chronic hypercapnic respiratory failure. Some children could be transferred out of the intensive care unit and into home mechanical ventilation.

Impact of obesity and ovariectomy on respiratory function in female mice.

Obesity and the corresponding variations in female sex hormones are associated with severe lung disease. We determined the potential effects of obesity and sex hormones in female mice by investigating changes in lung structure and respiratory function in an obesity model induced by postnatal overnutrition. Obese female mice exhibited pronounced weight gain, abdominal fat accumulation and collagen type I deposition in the airways. However, neither elastic tissue nor estrogen receptors-α/-ß were affected in obese female mice after ovariectomy or sham-operated mice. Bronchoconstriction in response to methacholine challenge in obese sham-operated mice was higher than in the obese group after ovariectomy. Our results suggest that the coexistence of obesity and ovariectomy impacted on respiratory system and airway resistance (attenuates bronchoconstriction after methacholine), on collagen I deposition and on airway estrogen ß-receptors of mice.

Alterações posturais associadas a distúrbios respiratórios e sua correlação com as desordens temporomandibulares: uma revisão de literatura / Postural changes associated with respiratory disorders and their correlation with temporomandibular disorders: a literature review

Objetivo: a presente revisão almeja fornecer à prática clínico-odontológica e ao meio científico uma compreensão atualizada acerca da correlação entre as alterações posturais geradas pela presença de distúrbios respiratórios e as desordens temporomandibulares (DTMs). Revisão de literatura: foi realizada uma busca entre o período de 2005 a 2021 nas seguintes bases de dados: Medline (via PubMed), Portal de Periódicos Capes e Scopus, utilizando-se dos termos "temporomandibular joint; temporomandibular disorders; posture control; postural control; breathing". Como resultado, foram encontrados 4.384 documentos, que foram analisados por títulos, resumos, texto completo e critérios de elegibilidade, até se chegar ao total de 5 estudos a serem incluídos nesta revisão. Considerações finais: os principais fatores observados foram a associação das DTMs com condições como padrão de respiração do tipo bucal, postura anterior da cabeça, hiperatividade de músculos acessórios da respiração, rotação posterior da mandíbula e apneia obstrutiva do sono. Os estudos ressaltaram a necessidade da abordagem completa desses pacientes, visto que os papéis dos distúrbios respiratórios e das alterações posturais podem representar desafios no diagnóstico e no tratamento das DTMs.(AU)

Objective: this review aims to provide to the clinical dental practice and the scientific community an updated understanding of the correlation between postural changes generated by the presence of respiratory disorders and temporomandibular joint disorders (TMD). Literature review: a search was carried out covering the period from 2005 to 2021 in the following databases: Medline (via PubMed), Portal de Periódicos Capes and Scopus using the terms temporomandibular joint; temporomandibular disorders; posture control; postural control; breathing. As a result, 4,384 documents were obtained and shortlisted by title, abstracts, full text and eligibility criteria, resulting in the five studies included in this review. Final considerations: the main factors observed were the association of TMD with conditions as mouth breathing, anterior head posture, hyperactivity of accessory breathing muscles, posterior rotation of the jaw and obstructive sleep apnea. The studies underscored the need for a complete approach to these patients, given that the role of respiratory disorders and postural changes may represent a challenge in the diagnosis and treatment of TMD.(AU)

Fluid Dynamics of Respiratory Infectious Diseases.

The host-to-host transmission of respiratory infectious diseases is fundamentally enabled by the interaction of pathogens with a variety of fluids (gas or liquid) that shape pathogen encapsulation and emission, transport and persistence in the environment, and new host invasion and infection. Deciphering the mechanisms and fluid properties that govern and promote these steps of pathogen transmission will enable better risk assessment and infection control strategies, and may reveal previously underappreciated ways in which the pathogens might actually adapt to or manipulate the physical and chemical characteristics of these carrier fluids to benefit their own transmission. In this article, I review our current understanding of the mechanisms shaping the fluid dynamics of respiratory infectious diseases.

Paroxysmal dyspnea in Parkinson's disease: Respiratory dyskinesias and autonomic hyperventilation are not the same.

Respiratory complaints are not uncommon in patients with Parkinson's disease (PD). While many are explained by pulmonary and cardiovascular problems unrelated to PD, secondary effects of PD, such as kyphoscoliosis, respiratory muscle rigidity, repeated pneumonias, or side effects of medication such as dyskinesias, there is a small group of patients with paroxysmal dyspnea for whom neither anxiety or other explanation has been found. This Point of View was written to call attention to this neglected, uncommon, but very distressing symptom.

Eight months follow-up study on pulmonary function, lung radiographic, and related physiological characteristics in COVID-19 survivors.

To describe the long-term health outcomes of patients with COVID-19 and investigate the potential risk factors. Clinical data during hospitalization and at a mean (SD) day of 249 (15) days after discharge from 40 survivors with confirmed COVID-19 (including 25 severe cases) were collected and analyzed retrospectively. At follow-up, severe cases had higher incidences of persistent symptoms, DLCO impairment, and higher abnormal CT score as compared with mild cases. CT score at follow-up was positively correlated with age, LDH level, cumulative days of oxygen treatment, total dosage of glucocorticoids used, and CT peak score during hospitalization. DLCO% at follow-up was negatively correlated with cumulative days of oxygen treatment during hospitalization. DLCO/VA% at follow-up was positively correlated with BMI, and TNF-α level. Among the three groups categorized as survivors with normal DLCO, abnormal DLCO but normal DLCO/VA, and abnormal DLCO and DLCO/VA, survivors with abnormal DLCO and DLCO/VA had the lowest serum IL-2R, IL-8, and TNF-α level, while the survivors with abnormal DLCO but normal DLCO/VA had the highest levels of inflammatory cytokines during hospitalization. Altogether, COVID-19 had a greater long-term impact on the lung physiology of severe cases. The long-term radiological abnormality maybe relate to old age and the severity of COVID-19. Either absent or excess of inflammation during COVID-19 course would lead to the impairment of pulmonary diffusion function.

Cardiorespiratory findings in epilepsy: A recent review on outcomes and pathophysiology.

Epilepsy is a debilitating disorder of uncontrollable recurrent seizures that occurs as a result of imbalances in the brain excitatory and inhibitory neuronal signals, that could stem from a range of functional and structural neuronal impairments. Globally, nearly 70 million people are negatively impacted by epilepsy and its comorbidities. One such comorbidity is the effect epilepsy has on the autonomic nervous system (ANS), which plays a role in the control of blood circulation, respiration and gastrointestinal function. These epilepsy-induced impairments in the circulatory and respiratory systems may contribute toward sudden unexpected death in epilepsy (SUDEP). Although, various hypotheses have been proposed regarding the role of epilepsy on ANS, the linking pathological mechanism still remains unclear. Channelopathies and seizure-induced damages in ANS-control brain structures were some of the causal/pathological candidates of cardiorespiratory comorbidities in epilepsy patients, especially in those who were drug resistant. However, emerging preclinical research suggest that neurotransmitter/receptor dysfunction and synaptic changes in the ANS may also contribute to the epilepsy-related autonomic disorders. Thus, pathological mechanisms of cardiorespiratory dysfunction should be elucidated by considering the modifications in anatomy and physiology of the autonomic system caused by seizures. In this regard, we present a comprehensive review of the current literature, both clinical and preclinical animal studies, on the cardiorespiratory findings in epilepsy and elucidate the possible pathological mechanisms of these findings, in hopes to prevent SUDEP especially in patients who are drug resistant.

Lung function decline is associated with serum uric acid in Korean health screening individuals.

We performed a retrospective cohort study of 19,237 individuals who underwent at least three health screenings with follow-up periods of over 5 years to find a routinely checked serum marker that predicts lung function decline. Using linear regression models to analyze associations between the rate of decline in the forced expiratory volume in 1 s (FEV1) and the level of 10 serum markers (calcium, phosphorus, uric acid, total cholesterol, total protein, total bilirubin, alkaline phosphatase, aspartate aminotransferase, creatinine, and C-reactive protein) measured at two different times (at the first and third health screenings), we found that an increased uric acid level was significantly associated with an accelerated FEV1 decline (P = 0.0014 and P = 0.037, respectively) and reduced FEV1 predicted % (P = 0.0074 and P = 8.64 × 10-7, respectively) at both visits only in non-smoking individuals. In addition, we confirmed that accelerated forced vital capacity (FVC) and FEV1/FVC ratio declines were observed in non-smoking individuals with increased serum uric acid levels using linear mixed models. The serum uric acid level thus potentially predicts an acceleration in lung function decline in a non-smoking general population.

Unraveling the Mechanisms Underlying Irregularities in Inspiratory Rhythm Generation in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder anatomically characterized by a progressive loss of dopaminergic neurons in the substantia nigra compacta (SNpc). Much less known, yet clinically very important, are the detrimental effects on breathing associated with this disease. Consistent with the human pathophysiology, the 6-hydroxydopamine hydrochloride (6-OHDA) rodent model of PD shows reduced respiratory frequency (fR) and NK1r-immunoreactivity in the pre-Bötzinger complex (preBötC) and PHOX2B+ neurons in the retrotrapezoid nucleus (RTN). To unravel mechanisms that underlie bradypnea in PD, we employed a transgenic approach to label or stimulate specific neuron populations in various respiratory-related brainstem regions. PD mice were characterized by a pronounced decreased number of putatively rhythmically active excitatory neurons in the preBötC and adjacent ventral respiratory column (VRC). Specifically, the number of Dbx1 and Vglut2 neurons was reduced by 47.6% and 17.3%, respectively. By contrast, inhibitory Vgat+ neurons in the VRC, as well as neurons in other respiratory-related brainstem regions, showed relatively minimal or no signs of neuronal loss. Consistent with these anatomic observations, optogenetic experiments identified deficits in respiratory function that were specific to manipulations of excitatory (Dbx1/Vglut2) neurons in the preBötC. We conclude that the decreased number of this critical population of respiratory neurons is an important contributor to the development of irregularities in inspiratory rhythm generation in this mouse model of PD.SIGNIFICANCE STATEMENT We found a decreased number of a specific population of medullary neurons which contributes to breathing abnormalities in a mouse model of Parkinson's disease (PD).