Calcium-sensing receptor and CPAP-induced neonatal airway hyperreactivity in mice

Mayer, Catherine; Roos, B.; Teske, J.J.; Wells, Natalie; Martin, Richard J.; Chang, Wenhan; Pabelick, Christina M.; Prakash, Y. S.; MacFarlane, Peter M.

doi:10.1038/s41390-021-01540-4

Cited by 6 publications

(8 citation statements)

References 47 publications

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“…This is consistent with animal data suggesting that CPAP stimulates lung growth 33. Other animal data suggest that extended CPAP increases airway reactivity and the risk of wheezing in preterm infants 34 35…”

Section: Discussionsupporting

confidence: 87%

Extended CPAP or low-flow nasal cannula for intermittent hypoxaemia in preterm infants: a 24-hour randomised clinical trial

Yazdi,

Carlo,

Nakhmani

et al. 2024

Arch Dis Child Fetal Neonatal Ed

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ObjectiveOptimal timing of continuous positive airway pressure (CPAP) cessation in preterm infants remains undetermined. We hypothesised that CPAP extension compared with weaning to low-flow nasal cannula (NC) reduces intermittent hypoxaemia (IH) and respiratory instability in preterm infants meeting criteria to discontinue CPAP.DesignSingle-centre randomised clinical trial.SettingLevel 4 neonatal intensive care unit.Patients36 infants <34 weeks’ gestation receiving CPAP≤5 cmH2O and fraction of inspired oxygen (FiO2) ≤0.30 and meeting respiratory stability criteria.InterventionsExtended CPAP was compared with weaning to low-flow NC (0.5 L/kg/min with a limit of 1.0 L/min) for 24 hours.OutcomesThe primary outcome was IH (number of episodes with SpO2<85% lasting ≥10 s). Secondary outcomes included: coefficient of variability of SpO2, proportion of time in various SpO2ranges, episodes (≥10 s) with SpO2<80%, median cerebral and renal oxygenation, median effective FiO2, median transcutaneous carbon dioxide and bradycardia (<100/min for≥10 s).ResultsThe median (IQR) episodes of IH per 24-hour period was 20 (6–48) in the CPAP group and 76 (18–101) in the NC group (p=0.03). Infants continued on CPAP had less bradycardia, time with SpO2<91% and <85%, and lower FiO2(all p<0.05). There were no statistically significant differences in IH<80%, median transcutaneous carbon dioxide or median cerebral or renal oxygenation.ConclusionIn preterm infants meeting respiratory stability criteria for CPAP cessation, extended CPAP decreased IH, bradycardia and other hypoxaemia measures compared with weaning to low-flow NC during the 24-hour intervention.Trial registration numberNCT04792099.

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Section: Discussionsupporting

confidence: 87%

Extended CPAP or low-flow nasal cannula for intermittent hypoxaemia in preterm infants: a 24-hour randomised clinical trial

Yazdi,

Carlo,

Nakhmani

et al. 2024

Arch Dis Child Fetal Neonatal Ed

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“…By regulating airflow by constricting or relaxing airways, ASMCs were demonstrated to be involved in overproliferation in response to various factors, such as growth factors, cytokine inflammatory mediators, and enzymes, and to participate in airway remodeling, thereby exacerbating asthma 25 . Previous studies have found that increased airway CaSR expression in neonatal mice after CPAP was associated with a long‐term increase in airway responsiveness 10 . In addition, Yarova et al 11 found that CaSR was elevated in human (ages ranged from 40 to 80 years) and mouse (6‐week to 8‐week‐old C57/Bl6 mice) asthmatic ASMC, which may be caused by inflammatory cationic proteins correlated with asthma severity.…”

Section: Discussionmentioning

confidence: 99%

“…25 Previous studies have found that increased airway CaSR expression in neonatal mice after CPAP was associated with a longterm increase in airway responsiveness. 10 In addition, Yarova et al 11 found that CaSR was elevated in human (ages ranged from 40 to 80 years) and mouse (6-week to 8-week-old C57/Bl6 mice) asthmatic ASMC, which may be caused by inflammatory cationic proteins correlated with asthma severity. Indeed, we showed that the CaSR gene and protein expression levels were significantly elevated in the lung tissues of OVA-treated pups (4 weeks old).…”

Section: Comparison Of Inflammatory Factors and Chemokines Among Groupsmentioning

confidence: 99%

“…CaSR is widely distributed in the parathyroid glands, gastrointestinal tract, skin, brain, bone, heart, and immune cells 8 . At present, CaSR is known to be expressed in embryonic interstitial lungs 9 and thought to be involved in AHR in neonatal mice induced by noninvasive continuous positive airway pressure ventilation 10 . Moreover, CaSR promotes the proliferation of airway smooth muscle cells (ASMCs) to further trigger AHR, thus participating in the development of adult asthma 11,12 .…”

Section: Introductionmentioning

confidence: 99%

“…8 At present, CaSR is known to be expressed in embryonic interstitial lungs 9 and thought to be involved in AHR in neonatal mice induced by noninvasive continuous positive airway pressure ventilation. 10 Moreover, CaSR promotes the proliferation of airway smooth muscle cells (ASMCs) to further trigger AHR, thus participating in the development of adult asthma. 11,12 However, the involvement of CaSR in childhood asthma is unknown, prompting us to perform this in vivo study.…”

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confidence: 99%

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The role of calcium‐sensitive receptor in ovalbumin‐induced airway inflammation and hyperresponsiveness in juvenile mice with asthma

Xiang

Tao

2022

The Kaohsiung J of Med Scie

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The role of the calcium-sensitive receptor (CaSR) was assessed in a juvenile mouse model of asthma induced by ovalbumin (OVA). The experiment was divided into normal control, OVA, and OVA +2.5/5 mg/kg NPS2143 (a CaSR antagonist) groups. OVA induction was performed in all groups except the normal control, followed by assessing airway hyperresponsiveness (AHR) and lung pathological changes. Serum OVA-specific IgE and IgG1 were detected with an enzyme-linked immunosorbent assay (ELISA), and inflammatory cells were counted in bronchoalveolar lavage fluid (BALF). Real-time quantitative polymerase chain reaction, ELISA, and western blotting were performed to detect gene and protein expression. NPS2143 improved the OVA-induced AHR in mice, and AHR was higher in the OVA +2.5 mg/kg NPS2143 group than in the OVA +5 mg/kg NPS2143 group. Furthermore, NPS2143 reduced the production of OVAspecific IgE and IgG1 in serum and the number of eosinophils and lymphocytes in BALF in OVA mice with reduced CaSR expression in lung tissues. Besides, OVA-induced mice exhibited peribronchial and perivascular inflammatory cell infiltration, which was accompanied by severe goblet cell hyperplasia/hyperplasia and airway mucus hypersecretion. Furthermore, these mice exhibited increased levels of Interleukin (IL)-5, IL-13, MCP-1, and eotaxin, which were alleviated by NPS2143. The 5 mg/kg NPS2143 showed more effective than the 2.5 mg/kg treatment. CaSR expression was elevated in the lung tissues of OVA-induced asthmatic juvenile mice, whereas the CaSR antagonist NPS2143 reduced AHR and attenuated the inflammatory response in OVA-induced juvenile mice, possibly exerting therapeutic effects on childhood asthma.

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Interactions between calcium regulatory pathways and mechanosensitive channels in airways

Yao,

Borkar,

Zheng

et al. 2023

Expert Review of Respiratory Medicine

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Calcium-sensing receptor and CPAP-induced neonatal airway hyperreactivity in mice

Cited by 6 publications

References 47 publications

Extended CPAP or low-flow nasal cannula for intermittent hypoxaemia in preterm infants: a 24-hour randomised clinical trial

Extended CPAP or low-flow nasal cannula for intermittent hypoxaemia in preterm infants: a 24-hour randomised clinical trial

The role of calcium‐sensitive receptor in ovalbumin‐induced airway inflammation and hyperresponsiveness in juvenile mice with asthma

Interactions between calcium regulatory pathways and mechanosensitive channels in airways

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