Panic disorder respiratory subtype: psychopathology and challenge tests - an update

Panic disorder (PD) pathophysiology is very heterogeneous, and the discrimination of distinct subtypes could be very useful. A subtype based on respiratory symptoms is known to constitute a specific subgroup. However, evidence to support the respiratory subtype (RS) as a distinct subgroup of PD with a well-defined phenotype remains controversial. Studies have focused on characterization of the RS based on symptoms and response to CO2. In this line, we described clinical and biological aspects focused on symptomatology and CO2 challenge tests in PD RS. The main symptoms that characterize RS are dyspnea (shortness of breath) and a choking sensation. Moreover, patients with the RS tended to be more responsive to CO2 challenge tests, which triggered more panic attacks in this subgroup. Future studies should focus on discriminating respiratory-related clusters and exploring psychophysiological and neuroimaging outcomes in order to provide robust evidence to confirm RS as a distinct subtype of PD.

Dysfunctional breathing: what do we know? / Disfunção respiratória: o que sabemos?

ABSTRACT Dysfunctional breathing (DB) is a respiratory condition characterized by irregular breathing patterns that occur either in the absence of concurrent diseases or secondary to cardiopulmonary diseases. Although the primary symptom is often dyspnea or "air hunger", DB is also associated with nonrespiratory symptoms such as dizziness and palpitations. DB has been identified across all ages. Its prevalence among adults in primary care in the United Kingdom is approximately 9.5%. In addition, among individuals with asthma, a positive diagnosis of DB is found in a third of women and a fifth of men. Although DB has been investigated for decades, it remains poorly understood because of a paucity of high-quality clinical trials and validated outcome measures specific to this population. Accordingly, DB is often underdiagnosed or misdiagnosed, given the similarity of its associated symptoms (dyspnea, tachycardia, and dizziness) to those of other common cardiopulmonary diseases such as COPD and asthma. The high rates of misdiagnosis of DB suggest that health care professionals do not fully understand this condition and may therefore fail to provide patients with an appropriate treatment. Given the multifarious, psychophysiological nature of DB, a holistic, multidimensional assessment would seem the most appropriate way to enhance understanding and diagnostic accuracy. The present narrative review was developed as a means of summarizing the available evidence about DB, as well as improving understanding of the condition by researchers and practitioners.

RESUMO A disfunção respiratória (DR) é um quadro respiratório caracterizado por padrões respiratórios irregulares que ocorrem na ausência de doenças concomitantes ou secundariamente a doenças cardiopulmonares. Embora o principal sintoma seja frequentemente dispneia ou "fome por ar", a DR também está associada a sintomas não respiratórios, como vertigem e palpitações. A DR pode ser identificada em todas as idades. Sua prevalência entre adultos na atenção primária no Reino Unido é de aproximadamente 9,5%. Além disso, entre indivíduos com asma, um diagnóstico positivo de DR é encontrado em um terço das mulheres e um quinto dos homens. Embora a DR tenha sido investigada por décadas, ela permanece pouco compreendida devido a uma escassez de ensaios clínicos de alta qualidade e de variáveis de desfecho validadas especificamente para essa população. Assim, a DR é frequentemente subdiagnosticada ou diagnosticada incorretamente, devido à similaridade de seus sintomas associados (dispneia, taquicardia e vertigem) aos de outras doenças cardiopulmonares comuns, como DPOC e asma. As altas taxas de diagnóstico incorreto de DR sugerem que os profissionais de saúde não entendam completamente esse quadro e possam, portanto, não fornecer aos pacientes um tratamento adequado. Dada à natureza multifatorial e psicofisiológica da DR, uma avaliação holística e multidimensional parece ser a maneira mais apropriada de melhorar a compreensão e a precisão do diagnóstico. A presente revisão foi desenvolvida como um meio de resumir as evidências disponíveis sobre DB, bem como de melhorar a compreensão do quadro por pesquisadores e profissionais.

The role of hyperventilation: hypocapnia in the pathomechanism of panic disorder

OBJECTIVE: The authors present a profile of panic disorder based on and generalized from the effects of acute and chronic hyperventilation that are characteristic of the respiratory panic disorder subtype. The review presented attempts to integrate three premises: hyperventilation is a physiological response to hypercapnia; hyperventilation can induce panic attacks; chronic hyperventilation is a protective mechanism against panic attacks. METHOD: A selective review of the literature was made using the Medline database. Reports of the interrelationships among panic disorder, hyperventilation, acidosis, and alkalosis, as well as catecholamine release and sensitivity, were selected. The findings were structured into an integrated model. DISCUSSION: The panic attacks experienced by individuals with panic disorder develop on the basis of metabolic acidosis, which is a compensatory response to chronic hyperventilation. The attacks are triggered by a sudden increase in (pCO2) when the latent (metabolic) acidosis manifests as hypercapnic acidosis. The acidotic condition induces catecholamine release. Sympathicotonia cannot arise during the hypercapnic phase, since low pH decreases catecholamine sensitivity. Catecholamines can provoke panic when hyperventilation causes the hypercapnia to switch to hypocapnic alkalosis (overcompensation) and catecholamine sensitivity begins to increase. CONCLUSION: Therapeutic approaches should address long-term regulation of the respiratory pattern and elimination of metabolic acidosis.

OBJETIVO: Os autores apresentam um modelo de transtorno do pânico que se baseia nos efeitos da hiperventilação aguda e crônica, característicos do subtipo respiratório de transtorno do pânico. O modelo é generalizado a partir desses efeitos. Ele integra três características da hiperventilação: a hiperventilação é uma resposta fisiológica à hipercapnia; a hiperventilação pode induzir ataques de pânico; a hiperventilação crônica representa um mecanismo protetor contra os ataques de pânico. MÉTODO: Revisão seletiva da literatura a partir da base de dados Medline. Foram selecionados relatos referentes à inter-relação entre transtorno do pânico, hiperventilação, acidose, alcalose, liberação de catecolaminas e sensibilidade a catecolaminas, sendo os achados estruturados de modo a formar um modelo integrado. DISCUSSÃO: Os ataques de pânico do transtorno do pânico desenvolvem-se com base numa acidose metabólica, que é uma resposta compensatória à hiperventilação crônica. Os ataques são desencadeados por um súbito aumento da pressão parcial de dióxido de carbono (pCO2), quando a acidose (metabólica) latente se manifesta pela acidose hipercápnica. A condição acidótica induz liberação de catecolaminas. A simpaticotonia não pode manifestar-se durante a fase de hipercapnia, pois o baixo pH diminui a sensibilidade às catecolaminas. As catecolaminas podem provocar pânico quando a hipercapnia comuta para uma alcalose hipocápnica devido à supercompensação pela hiperventilação, situação na qual a sensibilidade às catecolaminas liberadas começa a aumentar. CONCLUSÃO: As abordagens terapêuticas deveriam voltar-se para a regulação em longo prazo do padrão respiratório e a eliminação da acidose metabólica.

Post-task changes in visual P300 and their reversibility through brief hyperventilation.

Long hours of continuous, mental task reportedly increase the average auditory P3 latency of the normal subjects significantly, a change that is thought to be related to mental fatigue. We have tried out several protocols of varying task difficulty and duration in an effort to study the onset of the assumed fatigue-related changes. The present study shows that changes in visual event-related potential occur in less than two minutes if the task is sufficiently rigorous. The changes occur both in latency and in amplitude. Moreover, the changes are reversible with a brief (30 second) period of hyperventilation. The changes were most marked at Fz. Following the difficult task, the P3 amplitude at Fz decreased from 8.588 micro/V +/- 0.966 to 5.800 microV +/- 0.795 and the P3 latency increased from 368 +/- 4 ms to 380 +/- 3. Following hyperventilation, the P3 amplitude at Fz reverted to 8.457 +/- 5 and the P3 latency reverted to 371 +/- 5 ms. These observations call for further investigations on the cause of the post-task changes and their quick reversibility.

Efecto de la maniobra inspiratoria y de la hiperinsuflación pulmonar en los flujos espiratorios máximos en pacientes con fibrosis quística / Effect of inspiratory maneuver and lung hyperinflation on maximal expiratory flow-volume curves in cystic fibrosis patients

El tiempo inspiratorio previo a la realización de una maniobra espiratoria forzada máxima (FEM) es una variable que no ha sido completamente estudiada en Fibrosis Quística (FQ). El objetivo de este estudio fue evaluar la hipótesis que niños con FQ tendrían mayores volúmenes y flujos espiratorios forzados al disminuir la duracion del tiempo inspiratorio. Se estudiaron 16 niños con FQ, en etapa estable, sin haber presentado una exacerbación respiratoria en los ultimos dos meses, (10 hombres), de edad 11,9 ñ 0,7 años (promedio ñ ES), con un FEV1 de 62,8 ñ 6,4 porciento predicho. Las pruebas de función pulmonar consistieron en la medición de volúmenes pulmonares estáticos y resistencia de la vía aérea, seguido de evaluación dinámica de la función pulmonar. Esta última medición fue precedida de 3 maniobras inspiratorias diferentes en forma aleatoria[inspiración y detención de 0 segundos (M0), 2 segundos (M2) o 5 segundos (M5)]. El grupo se dividió en pacientes con hiperinsuflación pulmonar detectada por VR/CPT > 30 porciento, (n=9) y sin hiperinsuflación pulmonar RV/CPT menor o igual 30 porciento (n=7). Los resultados demostraron que, en los pacientes con hiperinsuflación, VEF1 y CVF fueron 8,9 ñ 3,4 porciento (p<0,02) y 9,3 ñ 2,1 porciento (p > 0,001) mayores respectivamente, después de M0 en comparación a después de M2 y 2,4 ñ 2,8 porciento (p = ns) menor respectivamente después de M5 en relación a después de M2 (M0 vs M5:p<0,01 para ambos, VEF1 y CVF). En resumen, en pacientes portadores de fibrosis quística e hiperinsuflación, VEF1 y CVF son significativamente mayores luego de realizar una espiración sin detención de inspiración de 2 ó 5 segundos. Sugerimos que los mecanismos de relajación de la musculatura lisa del árbol bronquial pueden ser los responsables de este hallazgo

Associacao entre transtorno do panico, asma e outras doencas obstrutivas pulmonares / Association between panic disorder, asthma and other pulmonary obstructive disorders

A ocorrencia do transtorno do panico com asma e outras doencas obstrutivas pulmonares e maior que o esperado, baseando-se em suas prevalencias individuais...

Role of nitric oxide in hypoxia-induced hyperventilation and hypothermia: participation of the locus coeruleus

Hypoxia elicits hyperventilation and hypothermia, but the mechanisms involved are not well understood. The nitric oxide (NO) pathway is involved in hypoxia-induced hypothermia and hyperventilation, and works as a neuromodulator in the central nervous system, including the locus coeruleus (LC), which is a noradrenergic nucleus in the pons. The LC plays a role in a number of stress-induced responses, but its participation in the control of breathing and thermoregulation is unclear. Thus, in the present study, we tested the hypothesis that LC plays a role in the hypoxia-induced hypothermia and hyperventilation, and that NO is involved in these responses. Electrolytic lesions were performed bilaterally within the LC in awake unrestrained adult male Wistar rats weighing 250-350 g. Body temperature and pulmonary ventilation (VE) were measured. The rats were divided into 3 groups: control (N = 16), sham operated (N = 7) and LC lesioned (N = 19), and each group received a saline or an NG-nitro-L-arginine methyl ester (L-NAME, 250 µg/µl) intracerebroventricular (icv) injection. No significant difference was observed between control and sham-operated rats. Hypoxia (7 per cent inspired O2) caused hyperventilation and hypothermia in both control (from 541.62 + or - 35.02 to 1816.18 + or - 170.7 and 36.3 + or - 0.12 to 34.4 + or - 0.09, respectively) and LC-lesioned rats (LCLR) (from 694.65 + or - 63.17 to 2670.29 + or - 471.33 and 36 + or - 0.12 to 35.3 + or - 0.12, respectively), but the increase in VE was higher (P<0.05) and hypothermia was reduced (P<0.05) in LCLR. L-NAME caused no significant change in VE or in body temperature under normoxia, but abolished both the hypoxia-induced hyperventilation and hypothermia. Hypoxia-induced hyperventilation was reduced in LCLR treated with L-NAME. L-NAME also abolished the hypoxia-induced hypothermia in LCLR. The present data indicate that hypoxia-induced hyperventilation and hypothermia may be related to the LC, and that NO is involved in these responses.

Apoyo ventilatorio en pacientes con patología aguda del sistema nervioso central / Ventilatory support in patients with head injuries

Patients with severe head injury are prone to pulmonary complications that result in hypoxemia or hypercarbia, which could worsen their neurological condition. A rational ventilatory approach requires a good knowledge of respiratory and neurological pathophysiology. Airway management is of prime importance in neurological patients. Prophylactic chronic hyperventilation in head trauma is no longer recommended since it could impair cerebral perfusion, although transient hypocarbia could be of benefit to some patients. The use of low or moderate positive and expiratory pressure levels apparently improves oxygenation without worsening intracranial pressure. Ventilatory management should be closely monitored and adjusted to hemodynamic, respiratory and neurological status to achieve a good outcome

Atypical EEG pattern in children with absence seizures

Estudamos quatro crianças com o diagnóstico de crises de ausência (epilepsia generalizada primária) e com atividade delta generalizada no EEG, durante crises provocadas pela hiperpnéia. A ausência de descargas generalizadas por conplexos ponta-onda a 3 Hz, durante as crises de nossos pacientes, é achado incomum. Todas as crianças tiveram completo controle de suas crises com o valproato, assim como o desaparecimento das alteraçöes no EEG. Concluimos que a atividade delta generalizada observada no EEG de crianças durante a hiperpnéa nem sempre deve ser vista como achado normal, podendo ser um evento crítico da crise generalizada ausência

Pulmäo destruído por tuberculose: estudo funcional e radiológico de 30 casos / Pulmonary destruction due to tuberculosis: report of 30 cases

O objetivo deste trabalho foi o de correlacionar a quantidade de tecido pulmonar destruído com a funçäo respiratória e com a idade do paciente ao ser diagnosticada tuberculose, que variou entre 12 e 60 anos. Analisaram-se 30 doentes com destruiçäo de dois a 13 segmentos pulmonares avaliados através de radiografia simples de tórax. Funcionalmente, foram considerados restritivos 12 pacientes e obstrutivos 25 doentes. A análise da correlaçäo entre as variáveis para este grupo de indivíduos revelou que: 1 - a tuberculose adquirda em idade mais precoce levou a maior destruiçäo pulmonar, maior reduçäo da capacidade vital e da ventilaçäo voluntária máxima, mas näo influenciou nos parâmetros que indicam o grau de obstruçäo brónquica; 2 - quanto maior o número de segmentos destruídos, menor a capacidade vital e maior a freqüência respiratória em repouso, mas näo houve alteraçäo da ventilaçäo alveolar minuto dos fluxos pulmonares e nem da diferença alvéolo-arterial das pressöes de oxigênio

Effect of altered ventilations on human spinal and supra spinal reflexes.

The present study was aimed at evaluating the alterations in the human reflexes brought about by briefly altered ventilations. In 20 healthy young male volunteers, the H reflex and blink reflex were studied during normal ventilation, voluntary hypoventilation and voluntary hyperventilation. The latencies of these reflexes were compared. It was observed that the amount of altered ventilations used in the present study could not produce any significant change in these reflexes except in the case of the early response of the blink reflex.