BACKGROUND: Asthma is a common chronic inflammatory disease affecting more than 260 million people worldwide. Nocturnal exacerbations of asthma symptoms significantly affect sleep quality and contribute to the most serious asthma exacerbations, which can lead to respiratory failure or death. Although β2-adrenoceptor agonists are the standard of care for asthma, their bronchodilatory effect for nocturnal asthma is limited, and medications that specifically target symptoms of nocturnal asthma are lacking. HIGHLIGHT: Melatonin, which is secreted by the pineal gland, plays a crucial role in regulating circadian rhythms. Peak serum melatonin concentrations, which are inversely correlated with diurnal changes in pulmonary function, are higher in patients with nocturnal asthma than in healthy individuals. Melatonin potentiates bronchoconstriction through the melatonin MT2 receptor expressed in the smooth muscles of the airway and attenuates the bronchodilatory effects of β2-adrenoceptor agonists, thereby exacerbating asthma symptoms. Melatonin inhibits mucus secretion and airway inflammation, potentially ameliorating asthma symptoms. CONCLUSION: Melatonin may exacerbate or ameliorate various pathophysiological conditions associated with asthma. As a potential therapeutic agent for asthma, the balance between its detrimental effects on airway smooth muscles and its beneficial effects on mucus production and inflammation remains unclear. Further studies are needed to elucidate whether melatonin worsens or improves asthma symptoms.

Noonan syndrome (NS) is a genetic disorder characterized by craniofacial dysmorphism, chest deformities, congenital heart defects, and bleeding disorders. Although patients with NS have a high prevalence of orofacial deformity, few reports are available on their anesthetic management during orthognathic surgery. This case report describes a 31-year-old female with NS, anemia, hypertrophic cardiomyopathy, and mild mitral valve regurgitation who experienced severe bleeding during orthognathic surgery. After treating her anemia with oral iron therapy and subcutaneous epoetin β, 4 units of autologous blood was deposited prior to surgery. General anesthesia was induced with remifentanil and propofol and maintained with sevoflurane, remifentanil, and fentanyl. Despite mild hypotensive anesthesia (targeted mean arterial pressure of 65 mm Hg) with nitroglycerine and intravenous tranexamic acid for bleeding, adequate hemostasis was difficult to achieve and led to severe blood loss (1442 mL). Therefore, the 4 units of autologous blood and 2 units of packed red blood cells were transfused. Her postoperative course proceeded uneventfully without abnormal postoperative bleeding. Because patients with NS can have difficulty with hemostasis, vascular malformations, and fragile blood vessels, extensive hematologic evaluation and thorough preparation for unexpected bleeding are crucial to accomplish orthognathic surgery.

Nocturnal asthma is characterized by heightened bronchial reactivity at night, and plasma melatonin concentrations are higher in patients with nocturnal asthma symptoms. Numerous physiological effects of melatonin are mediated via its specific G protein-coupled receptors (GPCRs) named the MT1 receptor, which couples to both Gq and Gi proteins, and the MT2 receptor, which couples to Gi. We investigated whether melatonin receptors are expressed on airway smooth muscle; whether they regulate intracellular cyclic AMP (cAMP) and calcium concentrations ([Ca2+]i), which modulate airway smooth muscle tone; and whether they promote airway smooth muscle cell proliferation. We detected the mRNA and protein expression of the melatonin MT2 but not the MT1 receptor in native human and guinea pig airway smooth muscle and cultured human airway smooth muscle (HASM) cells by RT-PCR, immunoblotting, and immunohistochemistry. Activation of melatonin MT2 receptors with either pharmacological concentrations of melatonin (10-100 µM) or the nonselective MT1/MT2 agonist ramelteon (10 µM) significantly inhibited forskolin-stimulated cAMP accumulation in HASM cells, which was reversed by the Gαi protein inhibitor pertussis toxin or knockdown of the MT2 receptor by its specific siRNA. Although melatonin by itself did not induce an initial [Ca2+]i increase and airway contraction, melatonin significantly potentiated acetylcholine-stimulated [Ca2+]i increases, stress fiber formation through the MT2 receptor in HASM cells, and attenuated the relaxant effect of isoproterenol in guinea pig trachea. These findings suggest that the melatonin MT2 receptor is expressed in ASM, and modulates airway smooth muscle tone via reduced cAMP production and increased [Ca2+]i.

Ring 18 syndrome or ring chromosome 18 is an extremely rare genetic disorder involving the fusion of the 18th chromosomal ends to form a ring, often with genetic material loss of varying degrees. Although clinical presentation can be extremely variable, characteristic features usually include craniofacial malformations, delayed development, hypotonia, and other skeletal and congenital heart defects. We report the management of a 20-year-old male with ring chromosome 18 who underwent general anesthesia for dental treatment. Clinical manifestations for this patient included intellectual disability, short stature, hypertelorism, flat nasal bridge, micrognathia, a "carp-shaped" mouth, and aortic and pulmonary valve regurgitation. Although mask ventilation and oral intubation were easily performed, nasal intubation was difficult because of rhinostenosis. When providing general anesthesia for a patient with ring chromosome 18, anesthesiologists should evaluate the patient preoperatively for congenital heart defects and prepare for a potential difficult airway.