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SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S–specific total and neutralizing antibody responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19–vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing antibody against D614G, Delta (B.1.617.2), and Omicron BA.1.1 in the BAL compared with COVID-19 convalescents despite robust S-specific antibody responses in the blood. Furthermore, mRNA vaccination induced circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing antibody responses, especially against SARS-CoV-2 Omicron BA.1.1 in mice; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses not only against the ancestral virus but also the Omicron BA.1.1 variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during reinfection, but offer limited protection against breakthrough infection, especially by the Omicron sublineage. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by the Omicron sublineage and future VOCs.

BACKGROUND Although airway inflammation plays a major role in the pathophysiology of asthma, quantitative markers of airway inflammation are limited in clinical practice. OBJECTIVE To determine if levels of noninvasive markers of eosinophil-catalyzed oxidation, lipid peroxidation, and nitric oxide production are associated with asthma. METHODS Participants were enrolled from academic medical centers participating in the Severe Asthma Research Program. Clinical characteristics, laboratory data, pulmonary function tests, and levels of the following noninvasive markers were obtained: urinary bromotyrosine, a marker of eosinophil-catalyzed oxidation; urinary F(2)-isoprostanes, markers of lipid peroxidation; and exhaled nitric oxide, a marker of airway inflammation RESULTS Fifty-seven asthmatic participants and thirty-eight healthy participants were enrolled. Bromotyrosine, F(2)-isoprostanes, and exhaled nitric oxide were each significantly increased in asthmatic participants versus controls (p

Purpose of review Gastroesophageal reflux disease (GERD) is common in children with asthma and may be present with or without symptoms. Clinicians, influenced by position statements in national guidelines, have routinely treated children with poorly controlled asthma with various anti-GERD medications. This practice is based on the pervasive but unproven belief that GERD is an important determinant of poor asthma control. Recent findings Clinical studies show that GERD is highly prevalent in children with asthma, with estimates as high as 80%, but nearly half of the children are asymptomatic. However, there is no conclusive evidence per se that asymptomatic GERD informs asthma control, and treatment of GERD in the few controlled trials available for review does not substantively improve asthma outcomes. In a recent large controlled clinical trial, treatment with a proton-pump inhibitor (PPI) was not only ineffective, but adverse effects were common, including an increased prevalence of symptomatic respiratory infections. Summary Current evidence does not support the routine use of anti-GERD medications in the treatment of poorly controlled asthma of childhood. However large controlled trials of children symptomatic of both GERD and asthma have not been conducted, and in this case the benefits of treatment, although unproven, might outweigh the risks.

Critically ill children treated with extracorporeal membrane oxygenation (ECMO) support frequently have respiratory complications amenable to evaluation by flexible bronchoscopy (FB). The safety and efficacy of FB in this setting has not been well described in children.Retrospective analysis of 153 FBs in 79 children treated with ECMO at a single institution from 2000 to 2008. Demographic data, clinical findings, and complications were obtained. Chest radiographs reports were evaluated prior to and following FB. Physiologic variables were compared prior to and following FB.Seventy-nine patients underwent FB on ECMO [58 veno-venous (VV) and 21 veno-arterial (VA) ECMO], with 153 total FBs performed. Indications for FB included clearance of tenacious airway secretions (n = 118, 77%), or evaluation of suspected secondary infections with bronchoalveolar lavage (n = 26, 17%). Two patients also had surfactant instillation following secretion removal. FB was performed a median 5 days following cannulation for ECMO (range 2-14 days). Most common findings included thick secretions (n = 77, 50.3%), mucoid secretions (n = 15, 9.8%), and mucopurulent secretions (n = 28, 18.3%). No deterioration in radiographic lung findings was described post-FB. FB was not associated with any significant change in heart rate, systemic blood pressure, or temperature. No significant changes in ECMO pump flow rate or sweep gas flow was seen during or after FB. Cannula dislodgement, inadvertent extubation, fever, pneumothorax, or intraprocedural hypoxemia was not reported. Fifty-three FBs (35%) resulted in blood-tinged secretions from the endotracheal tube post-FB, which resolved spontaneously. Three patients received high frequency oscillatory ventilation (HFOV) following FB in association with mild hemorrhage.FB is a well-tolerated and safe procedure in critically ill pediatric patients on ECMO. FB may have a diagnostic as well as therapeutic benefit in such patients.

Summary Sulfasalazine has been associated with bronchopulmonary complications of inflammatory bowel disease (IBID) in adults. We describe a 12 year old boy who developed desquamative interstitial pneumonitis and hepatic cirrhosis several years following the onset of ulcerative colitis. The restrictive lung disease progressed despite cessation of sulfasalazine and initiation of corticosteroid therapy. We discuss a variety of bronchopulmonary complications of IBD and their association with sulfasalazine.

To study the effects of furosemide on the neonatal pulmonary circulation in the presence of lung injury, we measured pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, and concentrations of protein in lymph and plasma of nine lambs that received furosemide, 2 mg/kg iv, during a continuous 8-h intravenous infusion of air. Air embolism increased pulmonary vascular resistance by 71% and nearly tripled steady-state lung lymph flow, with no change in lymph-to-plasma protein ratio. These findings reflect an increase in lung vascular protein permeability. During sustained lung endothelial injury, diuresis from furosemide led to a rapid reduction in cardiac output (average 29%) and a 2-Torr decrease in left atrial pressure. Diuresis also led to hemoconcentration, with a 15% increase in both plasma and lymph protein concentrations. These changes were associated with a 27% reduction in lung lymph flow. In a second set of studies, we prevented the reduction in left atrial pressure after furosemide by inflating a balloon catheter in the left atrium. Nevertheless, lymph flow decreased by 25%, commensurate with the reduction in cardiac output that occurred after furosemide. In a third series of experiments, we minimized the furosemide-related decrease in cardiac output by opening an external fistula between the carotid artery and jugular vein immediately after injection of furosemide. In these studies, the reduction in lung lymph flow (average 17%) paralleled the smaller (17%) decrease in cardiac output. These results suggest that changes in lung vascular filtration pressure probably do not account for the reduction in lung lymph flow after furosemide in the presence of lung vascular injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Osteomyelitis of the sacroiliac joint is an uncommon pediatric infection. Technetium Tc 99m medronate scanning has been advocated as a sensitive diagnostic test. We present a case of Pseudomonas putrefaciens sacroiliac osteomyelitis that was not demonstrable using this technique but was detected by a gallium citrate Ga 67 scan. Report of a Case .—A 17-year-old Greek girl with thalassemia major had been receiving nightly subcutaneous deferoxamine mesylate infusions. Since splenectomy at the age of 10, she had taken daily prophylactic penicillin G potassium. She was admitted to the hospital with a two-day history of fever, chills, nausea, vomiting, and pain in the lower part of the back. Results of a physical examination were normal, as was a complete blood cell count. Results of urinalysis were normal and a chest roentgenogram showed no infiltrates. Blood cultures were obtained. She became afebrile by the next morning and because a nonproductive cough had

To study the effect of pulmonary perfusion on fluid filtration in the newborn lung, we measured pulmonary vascular pressures, cardiac output, lung lymph flow, and concentrations of protein in lymph and plasma of nine healthy, awake lambs, 2–3 wk old, before and during sustained alterations in pulmonary blood flow. A 12% reduction in cardiac output (from partial occlusion of the inferior vena cava) led to a corresponding decrease in lymph flow, consistent with a reduction in net lung fluid filtration. A 20% increase in pulmonary blood flow (from opening an external shunt between the carotid artery and jugular vein) increased lymph flow by approximately 40%, without a significant change in lymph protein concentration. These findings suggest that lung microvascular surface area expanded in response to increased perfusion, with little or no change in filtration pressure. In five lambs, lung microvascular pressure was increased by inflating a balloon catheter in the left atrium to establish full patency of the pulmonary microcirculation. In the presence of left atrial pressure elevation, increased perfusion through the arteriovenous shunt had no significant effect on pulmonary vascular pressures or lymph flow. Thus, in young lambs, modest changes in pulmonary blood flow may affect lung fluid filtration by altering perfused microvascular surface area; this response is inhibited in the presence of left atrial hypertension.

Muscle fatigue shifts the power spectrum of the diaphragmatic electromyogram (DE) from high to low frequencies. Hypoxia and hypercapnia accompany respiratory failure in neonates, however their contribution to respiratory muscle fatigue is unknown. We tested the effects of alveolar hypoxia and hypercapnia on the DE frequency spectrum in 5 preterm infants studied at 39 ± 2 post-conceptional weeks of age while they breathed room air (control) and after 5 minutes of breathing 17% O2 or 4% CO2. We recorded DE from bipolar electrodes at the right costal margin mid-axillary line, abdominal movements with a circumferential strain gauge, skin-surface O2 (PsO2) and CO2 (PsCO2), and esophageal pressure (Pes) with a saline-filled tube. A fast Fourier transform calculated the centroid frequency (Fc) and summed amplitudes of power (SA) over 256 ms windows of DE selected at the peak of abdominal respiratory movements, free of QRS complexes. In each infant, diaphragmatic SA and Pes excursions increased during both hypoxia and hypercapnia. Fc fell with hypoxia but not with hypercapnia: (X ± SE; *p

In adult sheep intravenous infusion of a 10% lipid emulsion at an hourly rate of 0.25 g/kg body weight increases pulmonary microvascular pressure and filtration of fluid into the lungs, causing pulmonary lymph flow to double (J Clin Invest 61:1291, 1978). As 10% lipid usually is administered at lower rates in infants, some of whom have lung disease, we tested the effect on lung fluid balance of a continuous parenteral infusion of 10% fat emulsion at an hourly rate of 0.125 g/kg in healthy, awake newborn lambs. We measured mean pulmonary arterial (Ppa) and left atrial (Pla) pressures, arterial blood gas tensions (PaO2 and PaCO2), lung blood flow (Qb) and lymph flow (Q1), and protein concentrations in lymph (PR1) and plasma (PRp) of 5 lambs, 1 to 3 wks old. After a 2-3 h infusion of isotonic saline (control), the lambs received an infusion of 10% lipid for 3-4 h at the same rate as the preceding saline. Results (X ± sx; *p < 0.05): Lipid infusion at a rate suitable for infants increased pulmonary microvascular pressure and lung lymph flow, and decreased lymph protein concentration, suggesting that intravenous fat causes constriction of the pulmonary circulation distal to sites of microvascular fluid exchange in lambs. Lipid infusions may thereby contribute to lung edema and impair arterial oxygenation.

Lung liquid volume in fetal lambs decreases before birth, as systemic arterial pressure and plasma protein concentration increase (Bland et al, J Appl Physiol 53:992, 1982). These developments may be the result of hormonal changes that occur late in gestation. Plasma concentrations of vasopressin increase several hours before birth in fetal lambs (Stark et al, Biol Neonate 35: 235, 1979) and intravenous infusion of arginine vasopressin causes reabsorption of fetal lung liquid (Perks & Cassin, Chest 81:63S, 1982). In chronic studies of 9 fetal lambs we found that plasma vasopressin, measured by radioimmunoassay, increased from 2.3± .4 pg/ml before labor to 37.2±9.2 pg/ml late in labor. In lambs killed during labor, there was an inverse relationship between lung water content and plasma vasopressin concentration. To see if this hormone might contribute to the prenatal decrease in fetal lung liquid, we intravenously infused either arginine vasopress in (treated) or isotonic saline (control) for 8 h in 4 sets of twin fetal lambs at 90-95% of term gestation. Plasma vasopressin concentrations in treated lambs were similar to those measured in lambs during labor. Infusion of vasopressin increased systemic arterial pressure by 9±3 torr and plasma protein concentration by 3±1 mg/ml. Extravascular lung water, measured gravimetrically, was significantly less in treated twins than in controls (11.9±1.0 vs 13.8±1.0 g/g dry lung). Thus, vasopressin may contribute to the hemodynamic changes and reduction in lung liquid that occur in lambs before birth.