Collagen VI is a key component of the extracellular matrix. Murine models suggest that it regulates Schwann cell differentiation, peripheral nerve myelination and regeneration after injury. Neuropathic findings in COL6-related dystrophies (COL6-RDs) have been rarely reported, often based on electromyography findings without nerve conduction abnormalities. We report 37 patients (1.5-79 years), from 32 different families, carrying the COL6A3-c.7447A>G variant, presenting with neuropathic/neuromyopathic findings. Most patients presented in the first decade of life with an abnormal gait and frequent falls (54%), delayed motor milestones (32%) and foot deformities (19%). Predominant distal weakness was present in 46% of patients, whereas 27% exhibited proximo-distal involvement. Foot deformities were present in 32%; joint contractures were present in 83%, exclusively affecting lower limbs in 49%. At last evaluation, mild restrictive respiratory insufficiency was diagnosed in 1 patient and nocturnal hypoventilation requiring non-invasive ventilation in 2. Most patients (89%) remained ambulant at last assessment. Nerve conduction studies (n=29) revealed reduced lower-limb CMAP amplitudes in 79%. Needle EMG (n=31) revealed chronic neurogenic-like features in 84% and mixed neuromyogenic features in 13%. Muscle biopsy (n=12) demonstrated features suggestive of neuropathic involvement in 4 (33%) and mixed neuropathic-myopathic features in 5 (42%). Muscle imaging (n=23) revealed a typical COL6-RD pattern in 48% (with severe distal lower limb atrophy in 65%), and isolated or predominant distal atrophy in 30%. Inheritance was autosomal recessive in all cases. The COL6A3-c.7447A>G variant was present in homozygosity in 24 (65%) and in compound heterozygosity with a second COL6A3 variant in 13 (35%), including 8 previously unreported. We report an expanding phenotypic spectrum associated with COL6-RD, underscoring its relevance in the diagnostic evaluation of distal motor neuropathy-like or neuromyopathic presentations.

Noninvasive ventilation (NIV) is a cornerstone therapy for chronic hypercapnic respiratory failure arising from chronic obstructive pulmonary disease (COPD), obesity hypoventilation syndrome (OHS), and neuromuscular disease (NMD). This article reviews the pathophysiology of ventilatory pump failure, key NIV mode features (continuous positive airway pressure, bilevel positive airway pressure-S/ST, volume-assured pressure support, auto-expiratory positive airway pressure), and advanced settings that govern patient-ventilator synchrony. It contrasts respiratory assist devices with home mechanical ventilators and links device choice to disease-specific needs.

ROHHAD is a rare, life-threatening paediatric disorder often overlooked and misdiagnosed. Chronic unexplained hypoventilation in children should raise suspicion. Early recognition and diagnosis are crucial to enable timely treatment and improve prognosis. https://bit.ly/4drYzWY.

Blood gas analysis is a commonly used diagnostic tool to evaluate the partial pressures of gas in blood and acid-base content. Understanding and using blood gas analysis enables providers to interpret respiratory, circulatory, and metabolic disorders.  A "blood gas analysis" can be performed on blood obtained from anywhere in the circulatory system (artery, vein, or capillary). An arterial blood gas (ABG) explicitly tests blood taken from an artery. ABG analysis assesses the patient's partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2). PaO2 provides information on the oxygenation status, and PaCO2 offers information on the ventilation status (chronic or acute respiratory failure). PaCO2 is affected by hyperventilation (rapid or deep breathing), hypoventilation (slow or shallow breathing), and acid-base status. Although oxygenation and ventilation can be assessed non-invasively via pulse oximetry and end-tidal carbon dioxide monitoring, respectively, ABG analysis is the standard.  When assessing the acid-base balance, most ABG analyzers measure the pH and PaCO2 directly. A derivative of the Hasselbach equation calculates the serum bicarbonate (HCO3) and base deficit or excess. This calculation frequently results in a discrepancy from the measured value due to the blood CO2 unaccounted for by the equation. The measured HCO3 uses a strong alkali that liberates all CO2 in serum, including dissolved CO2, carbamino compounds, and carbonic acid. The calculation only accounts for dissolved CO2; this measurement uses a standard chemistry analysis and will likely be called a "total CO2". Therefore, the difference will amount to around 1.2 mmol/L. However, a more considerable difference may be seen in the ABG compared to the measured value, especially in critically ill patients. The calculation has been disputed as both accurate and inaccurate based on the study, machine, or calibration used and must be interpreted appropriately based on institutional standards. Emergency medicine, intensivist, anesthesiology, and pulmonology clinicians frequently order arterial blood gases, which may also be used in other clinical settings. Healthcare professionals evaluate many diseases using an ABG, including acute respiratory distress syndrome (ARDS), severe sepsis, septic shock, hypovolemic shock, diabetic ketoacidosis, renal tubular acidosis, acute respiratory failure, heart failure, cardiac arrest, asthma, and inborn errors of metabolism.

Hypothyroidism affects a large subset of the population, with many undiagnosed. In iodine-sufficient regions, chronic autoimmune thyroiditis (Hashimoto's) is the leading cause. Chronic, untreated hypothyroidism can result in multisystem complications, including cardiovascular disease, infertility, and respiratory failure. The most severe presentation, myxedema, is a medical emergency marked by altered mentation, ranging from lethargy to coma, hypothermia, and hypoventilation. Prompt recognition and treatment with thyroid hormone replacement are essential to improve outcomes. We present a case of hypercapnic respiratory failure secondary to myxedema coma. A 51-year-old female with morbid obesity (BMI 39.9 kg/m[2]) presented unresponsive, hypoxemic, and cyanotic, requiring emergent intubation. Labs revealed severe anemia (Hb 6.5 g/dL) and respiratory acidosis. The urinalysis was positive for infection, and the urine culture grew Escherichia (E.) coli. Imaging showed small pericardial and pleural effusions, and echocardiography revealed preserved ejection fraction (55%). Thyroid studies confirmed severe hypothyroidism with thyroid-stimulating hormone (TSH) 38.2 mIU/L and free thyroxine (T4) < 0.07 ng/dL, consistent with myxedema coma. She was managed with IV levothyroxine, IV hydrocortisone, antibiotics, ventilatory support, diuresis, and electrolyte repletion. Following thyroid hormone therapy, her respiratory status and mentation improved, allowing extubation and discharge after 14 days on 2 L home oxygen. Myxedema coma-induced hypercapnic respiratory failure occurs through reduced central respiratory drive, respiratory muscle weakness, and impaired gas exchange from pleural effusions or pneumonia. Studies have shown diminished maximal inspiratory and expiratory pressures in hypothyroid patients, reversible with hormone replacement. Pericardial effusion, observed in up to one-third of severe hypothyroid cases, results from increased capillary permeability and typically resolves with levothyroxine therapy without invasive intervention. Hypercapnic respiratory failure secondary to myxedema coma is rare but life-threatening. Early diagnosis and thyroid hormone replacement are essential to prevent morbidity and mortality. Clinical vigilance is required for patients with unexplained respiratory failure, particularly women with nonspecific hypothyroid symptoms. Ensuring medication adherence, thyroid function monitoring, and adequate respiratory support is vital for preventing recurrence and improving outcomes.

Delayed recognition and management of severe obesity and obesity hypoventilation syndrome may result in life-threatening respiratory failure and multi-organ complications requiring prolonged intensive care. In metabolically unstable patients, pre-existing obesity-related malnutrition may worsen despite obesity itself and contribute to increased mortality. Early multidisciplinary intervention is essential to reduce morbidity and healthcare burden.

Acute respiratory failure (ARF) often leads to ICU admission, ventilatory support, illness, and death. The usual classification into hypoxemic and hypercapnic types does not capture its full complexity. Precision medicine uses the concept of "treatable traits" to guide care based on traits that are clinically relevant, identifiable, measurable, and possibly changeable. Arterial carbon dioxide pressure (PaCO2) reflects factors like alveolar ventilation, dead space, respiratory mechanics, and how patients respond to ventilatory support. This makes it clinically relevant in selected situations. We carried out a scoping review using PRISMA-ScR and JBI guidelines to summarize evidence on hypocapnia and hypercapnia as prognostic, stratification, or clinically relevant variables during respiratory support. We searched PubMed/MEDLINE, ScienceDirect, and Web of Science (1994-2025), and checked references by hand. Thirty-four studies met our criteria and were grouped into four areas: pre-intubation or early acute presentation, non-invasive support (NIV/HFNC), invasive mechanical ventilation (IMV), and weaning or post-extubation. In summary, hypocapnia was linked to worse outcomes or failure of support in hypoxemic or cardiogenic cases. Hypercapnia helped identify patients who benefited from NIV, such as those with chronic obstructive pulmonary disease or obesity hypoventilation. For IMV, the effects depended on the presence and severity of acidosis and on its duration. Overall, PaCO2 showed context-dependent clinical relevance, acting mainly as a prognostic or stratification marker and, in narrower settings, as a variable that may inform monitoring or support decisions. This review provides a pragmatic framework for interpreting PaCO2 across respiratory support contexts and highlights the need for safe and clinically meaningful targets.

Acute chest syndrome (ACS) is a common pulmonary complication in children with sickle cell disease, defined by a new pulmonary infiltrate on imaging accompanied by fever and/or respiratory symptoms. ACS pathophysiology is multifactorial and incompletely understood, involving vaso-occlusion, pulmonary infarction, inflammation, hypoventilation, and infection-the latter being a frequent trigger in children. While most pediatric cases are mild, ACS can be life-threatening and requires prompt diagnosis and management to prevent progression into respiratory failure. Mild cases are managed with pain control, IV hydration, empiric antibiotics, incentive spirometry, and supplemental oxygen when needed. More severe cases may require simple or exchange transfusion to reduce hemoglobin S levels and limit further vaso-occlusion. ACS is associated with neurologic events and long-term pulmonary complications, making prevention a clinical priority. Disease-modifying therapies include hydroxyurea and chronic transfusion. This review summarizes current evidence on the pathophysiology, risk factors, clinical presentation, diagnosis, acute management, and preventative therapies for ACS in children.

Essential hypertension remains a major global health problem with poorly defined mechanisms. Increased vascular sympathetic activity and sleep-disordered breathing are common features in hypertensive patients and adult spontaneously hypertensive rats (SHRs), an experimental model of essential hypertension. We hypothesized that SHRs exhibit inherent respiratory dysfunctions during postnatal development, leading to irregular breathing and hypoxaemia that contribute to later sympathetic hyperactivity. We assessed pulmonary ventilation, oxygen consumption, systemic and tissue oxygen levels and cardiovascular parameters in male and female normotensive (Wistar-Kyoto and Sprague-Dawley, NT) rats and SHRs from birth to adulthood. Newborn SHRs (0-2 days old) exhibited hypoventilation, fluctuating respiratory frequency and increased episodes of apnoea and breath-hold, resulting in hypoxaemia and reduced brain oxygen levels in comparison to NT pups. These irregularities and hypoxaemia persisted until postnatal day 12. During hypoxic challenges, SHR pups from 0 to 12 days of life displayed an impaired ventilatory response, contrasting with the developmental increase in hypoxic ventilatory response seen in NT animals. In adult animals, the higher mean arterial pressure levels in SHRs were correlated with postnatal hypoventilation, suggesting a developmental link between postnatal respiratory dysfunction and hypertension. Chronic exposure to hyperoxia (50% O2) during the first 2 weeks of life attenuated respiratory irregularities in neonatal SHRs and reduced sympathetic vasoconstrictor tone in adult SHRs. Our results show that SHRs show early-life respiratory deficits that lead to breathing irregularities and hypoxaemia during postnatal development, which might contribute to the development of sympathetic hyperactivity in essential hypertension. KEY POINTS: Arterial hypertension is a common cardiovascular disease globally; however, its underlying mechanisms are still not fully understood. In spontaneously hypertensive rats (SHRs), a widely used experimental model of arterial hypertension, we identified inherent respiratory dysfunctions that cause breathing irregularities during the postnatal period. Neonatal SHR pups exhibit hypoventilation, fluctuating respiratory frequency and increased episodes of apnoea and breath-hold, leading to hypoxaemia and reduced oxygen levels in the brain. Exposure to high oxygen levels during postnatal life attenuates the respiratory irregularities in neonatal SHRs and reduces sympathetic vasoconstrictor tone in adult SHRs. Our study shows that early-life respiratory irregularities and hypoxaemia are present in SHRs from birth and might contribute to the development of sympathetic hyperactivity in arterial hypertension.