A breathable gas inlet control device permits flow regulation at the inlet of a flow generator for a respiratory treatment apparatus such as a ventilator or continuous positive airway pressure device. The device may implement a variable inlet aperture size based on flow conditions. In one embodiment, an inlet flow seal opens or closes the inlet to a blower in accordance with changes in pressure within a seal activation chamber near the seal. The seal may be formed by a flexible membrane. A controller selectively changes the pressure of the seal activation chamber by controlling a set of one or more flow control valves to selectively stop forward flow, prevent back flow or lock open the seal to permit either back flow or forward flow. The controller may set the flow control valves as a function of detected respiratory conditions based on data from pressure and/or flow sensors.

A system provides warm, humidified gas to a patient via a patient interface. Horizontal connections can be used between the humidification chamber and conduit. To reduce the likelihood of condensate flowing back to the humidification chamber, or dead space or gases recirculation regions occurring within the gases flow path, a raised portion is positioned inside of the flow path to improve flow characteristics and to provide a barrier for condensate back flow. The raised portion also reduces the amount of condensate that is formed in the system and provides better flow characteristics for sensing purposes.

An example method for detecting respiratory disturbances experienced by a subject can include receiving an airflow signal and at least one of an acoustic or vibration signal, where the airflow, acoustic, and/or vibration signals are associated with the subjects breathing. At least one feature can be extracted from the airflow signal and at least one feature can be extracted from at least one of the acoustic or vibration signal. Based on the extracted features, at least one respiratory disturbance can be detected. The respiratory disturbance can be flow limited breath or inspiratory flow limitation (“IFL”).

Several embodiments of straps and headgear assemblies are described. Some of the embodiments provide straps that can had varied elasticity over the length of the straps. Some of the embodiments provide adjustment mechanisms that facilitate customization of headgear to a user.

Methods, systems, and apparatuses are described that indicate an amount at which various gas flow rates should be manually adjusted in order to achieve targeted total flow rates and concentration levels.

The invention relates to the field of virology. The invention provides an isolated essentially mammalian negative-sense single-stranded RNA virus (MPV) within the subfamily Pneumovirinae of the family Paramyxoviridae and identifiable as phylogenetically corresponding to the genus Metapneumovirus and components thereof.

A new respiratory clinic is expected to open in Wodonga next week to assess patients with fever and respiratory symptoms who meet the government criteria for COVID-19 testing.

Coenzyme Q (Qn) is a vital lipid component of the electron transport chain that functions in cellular energy metabolism and as a membrane antioxidant. In the yeast Saccharomyces cerevisiae, coq1–coq9 deletion mutants are respiratory-incompetent, sensitive to lipid peroxidation stress, and unable to synthesize Q6. The yeast coq10 deletion mutant is also respiratory-deficient and sensitive to lipid peroxidation, yet it continues to produce Q6 at an impaired rate. Thus, Coq10 is required for the function of Q6 in respiration and as an antioxidant and is believed to chaperone Q6 from its site of synthesis to the respiratory complexes. In several fungi, Coq10 is encoded as a fusion polypeptide with Coq11, a recently identified protein of unknown function required for efficient Q6 biosynthesis. Because “fused” proteins are often involved in similar biochemical pathways, here we examined the putative functional relationship between Coq10 and Coq11 in yeast. We used plate growth and Seahorse assays and LC-MS/MS analysis to show that COQ11 deletion rescues respiratory deficiency, sensitivity to lipid peroxidation, and decreased Q6 biosynthesis of the coq10Δ mutant. Additionally, immunoblotting indicated that yeast coq11Δ mutants accumulate increased amounts of certain Coq polypeptides and display a stabilized CoQ synthome. These effects suggest that Coq11 modulates Q6 biosynthesis and that its absence increases mitochondrial Q6 content in the coq10Δcoq11Δ double mutant. This augmented mitochondrial Q6 content counteracts the respiratory deficiency and lipid peroxidation sensitivity phenotypes of the coq10Δ mutant. This study further clarifies the intricate connection between Q6 biosynthesis, trafficking, and function in mitochondrial metabolism.

Coenzyme Q (Qn) is a vital lipid component of the electron transport chain that functions in cellular energy metabolism and as a membrane antioxidant. In the yeast Saccharomyces cerevisiae, coq1–coq9 deletion mutants are respiratory-incompetent, sensitive to lipid peroxidation stress, and unable to synthesize Q6. The yeast coq10 deletion mutant is also respiratory-deficient and sensitive to lipid peroxidation, yet it continues to produce Q6 at an impaired rate. Thus, Coq10 is required for the function of Q6 in respiration and as an antioxidant and is believed to chaperone Q6 from its site of synthesis to the respiratory complexes. In several fungi, Coq10 is encoded as a fusion polypeptide with Coq11, a recently identified protein of unknown function required for efficient Q6 biosynthesis. Because “fused” proteins are often involved in similar biochemical pathways, here we examined the putative functional relationship between Coq10 and Coq11 in yeast. We used plate growth and Seahorse assays and LC-MS/MS analysis to show that COQ11 deletion rescues respiratory deficiency, sensitivity to lipid peroxidation, and decreased Q6 biosynthesis of the coq10Δ mutant. Additionally, immunoblotting indicated that yeast coq11Δ mutants accumulate increased amounts of certain Coq polypeptides and display a stabilized CoQ synthome. These effects suggest that Coq11 modulates Q6 biosynthesis and that its absence increases mitochondrial Q6 content in the coq10Δcoq11Δ double mutant. This augmented mitochondrial Q6 content counteracts the respiratory deficiency and lipid peroxidation sensitivity phenotypes of the coq10Δ mutant. This study further clarifies the intricate connection between Q6 biosynthesis, trafficking, and function in mitochondrial metabolism.

Respiratory motion during the CT and PET parts of a PET/CT scan leads to imperfect alignment of anatomical features seen by the two modalities. In this work, we concentrate on the effects of motion during CT. We propose a novel approach for improving the alignment. Methods: Respiratory waveform data were gathered during the CT and PET parts of 28 PET/CT scans of cancer patients with 40 lesions up to 3 cm size in the lung or upper abdomen. PET list-mode data were reconstructed by three reconstruction methods: PET/static, PET/EX or end of expiration (OncoFreeze), and a novel PET/matched method that used both waveforms. The three methods were compared. The distance between tumor positions in PET and CT were characterized in visual interpretation by physicians as well as quantitatively. Tumor standardized uptake values (SUV_max and SUVpeak) were determined relative to SUV based on the static method. Image noise was evaluated in the liver and compared to PET/static. Results: In visual interpretation, the rate of good alignment was 13/21, 13/23 and 18/21 for PET/static, PET/EX and PET/matched methods, respectively, and the mean PET-CT distances were 3.5, 5.1 and 2.8 mm. In visual comparison with PET/EX, the rate of good alignment was increased in 1/10 and 7/10 cases for PET/static and PET/matched. SUV_max was on average 21% higher than PET/static when either PET/EX or PET/matched was used. SUVpeak was 12% higher. Image noise in the liver was 15% higher than static for the PET/EX method, and 40% higher for PET/matched; that is, noise was much lower than in gated PET. Conclusion: Acquiring respiratory waveforms both in PET (as in the current state of the art) and in CT (an unusual key step in this approach) has the potential to improve the alignment of PET and CT images. A proposed method for using this information was tested. Improved alignment was demonstrated.

Respiratory gating is the standard to overcome respiration effects degrading image quality in positron emission tomography (PET). Data-driven gating (DDG) using signals derived from PET raw data are promising alternatives to gating approaches requiring additional hardware. However, continuous bed motion (CBM) scans require dedicated DDG approaches for axially-extended PET, compared to DDG for conventional step-and-shoot scans. In this study, a CBM-capable DDG algorithm was investigated in a clinical cohort, comparing it to hardware-based gating using gated and fully motion-corrected reconstructions. Methods: 56 patients with suspected malignancies in thorax or abdomen underwent whole-body ¹⁸F-FDG CBM-PET/CT imaging using DDG and hardware-based respiratory gating (pressure-sensitive belt gating, BG). Correlation analyses were performed on both gating signals. Besides static reconstructions, BG and DDG were used for optimally-gated PET (BG-OG, DDG-OG) and fully motion-corrected PET (elastic motion correction; BG-EMOCO, DDG-EMOCO). Metabolic volumes, SUV_max and SUVmean of lesions were compared amongst the reconstructions. Additionally, the quality of lesion delineation in different PET reconstructions was independently evaluated by three experts. Results: Global correlation coefficients between BG and DDG signals amounted to 0.48±0.11, peaking at 0.89±0.07 when scanning the kidney and liver region. In total, 196 lesions were analyzed. SUV measurements were significantly higher in BG-OG, DDG-OG, BG-EMOCO and DDG-EMOCO compared to static images (P<0.001; median SUV_max: static, 14.3±13.4; BG-EMOCO, 19.8±15.7; DDG-EMOCO, 20.5±15.6; BG-OG, 19.6±17.1; DDG-OG, 18.9±16.6). No significant differences between BG-OG and DDG-OG, and BG-EMOCO and DDG-EMOCO, respectively, were found. Visual lesion delineation was significantly better in BG-EMOCO and DDG-EMOCO than in static reconstructions (P<0.001); no significant difference was found comparing BG and DDG (EMOCO, OG, respectively). Conclusion: DDG-based motion-compensation of CBM-PET acquisitions outperforms static reconstructions, delivering qualities comparable to hardware-based approaches. The new algorithm may be a valuable alternative for CBM-PET systems.

A data-driven method for respiratory gating in PET has recently been commercially developed. We sought to compare the performance of the algorithm to an external, device-based system for oncological [¹⁸F]-FDG PET/CT imaging. Methods: 144 whole-body [¹⁸F]-FDG PET/CT examinations were acquired using a Discovery D690 or D710 PET/CT scanner (GE Healthcare), with a respiratory gating waveform recorded by an external, device based respiratory gating system. In each examination, two of the bed positions covering the liver and lung bases were acquired with duration of 6 minutes. Quiescent period gating retaining ~50% of coincidences was then able to produce images with an effective duration of 3 minutes for these two bed positions, matching the other bed positions. For each exam, 4 reconstructions were performed and compared: data driven gating (DDG-retro), external device-based gating (RPM Gated), no gating but using only the first 3 minutes of data (Ungated Matched), and no gating retaining all coincidences (Ungated Full). Lesions in the images were quantified and image quality was scored by a radiologist, blinded to the method of data processing. Results: The use of DDG-retro was found to increase SUVmax and to decrease the threshold-defined lesion volume in comparison to each of the other reconstruction options. Compared to RPM-gated, DDG-retro gave an average increase in SUV_max of 0.66 ± 0.1 g/mL (n=87, p<0.0005). Although results from the blinded image evaluation were most commonly equivalent, DDG-retro was preferred over RPM gated in 13% of exams while the opposite occurred in just 2% of exams. This was a significant preference for DDG-retro (p=0.008, n=121). Liver lesions were identified in 23 exams. Considering this subset of data, DDG-retro was ranked superior to Ungated Full in 6/23 (26%) of cases. Gated reconstruction using the external device failed in 16% of exams, while DDG-retro always provided a clinically acceptable image. Conclusion: In this clinical evaluation, the data driven respiratory gating technique provided superior performance as compared to the external device-based system. For the majority of exams the performance was equivalent, but data driven respiratory gating had superior performance in 13% of exams, leading to a significant preference overall.

Coenzyme Q (Qn) is a vital lipid component of the electron transport chain that functions in cellular energy metabolism and as a membrane antioxidant. In the yeast Saccharomyces cerevisiae, coq1–coq9 deletion mutants are respiratory-incompetent, sensitive to lipid peroxidation stress, and unable to synthesize Q6. The yeast coq10 deletion mutant is also respiratory-deficient and sensitive to lipid peroxidation, yet it continues to produce Q6 at an impaired rate. Thus, Coq10 is required for the function of Q6 in respiration and as an antioxidant and is believed to chaperone Q6 from its site of synthesis to the respiratory complexes. In several fungi, Coq10 is encoded as a fusion polypeptide with Coq11, a recently identified protein of unknown function required for efficient Q6 biosynthesis. Because “fused” proteins are often involved in similar biochemical pathways, here we examined the putative functional relationship between Coq10 and Coq11 in yeast. We used plate growth and Seahorse assays and LC-MS/MS analysis to show that COQ11 deletion rescues respiratory deficiency, sensitivity to lipid peroxidation, and decreased Q6 biosynthesis of the coq10Δ mutant. Additionally, immunoblotting indicated that yeast coq11Δ mutants accumulate increased amounts of certain Coq polypeptides and display a stabilized CoQ synthome. These effects suggest that Coq11 modulates Q6 biosynthesis and that its absence increases mitochondrial Q6 content in the coq10Δcoq11Δ double mutant. This augmented mitochondrial Q6 content counteracts the respiratory deficiency and lipid peroxidation sensitivity phenotypes of the coq10Δ mutant. This study further clarifies the intricate connection between Q6 biosynthesis, trafficking, and function in mitochondrial metabolism.

Middle East respiratory syndrome (MERS) is an acute viral respiratory tract infection caused by the novel betacoronavirus. Cases have been limited to the Arabian Peninsula and its surrounding countries, and to travellers from the Middle East or their contacts. The clinical spectrum of infection varies from no symptoms or mild respiratory...

Acute respiratory distress syndrome was first described in 1967 and has become a defining condition in critical care. Around 40% of patients with ARDS will die, and survivors experience long term sequelae. No drug treatments exist for ARDS, however good supportive management reduces harm and improves outcome. In this podcast, John Laffey,...

A recorded webinar will stream April 27 outlining the Association’s interim recommendation for personal protective equipment in dental settings as some states consider loosening social distancing mandates.

Anakinra, a drug developed to treat rheumatoid arthritis might help patients who have developed acute respiratory distress syndrome caused by COVID-19, a small study published by The Lancet Rheumatology has found.

Nasal continuous positive airway pressure (NCPAP) has been the initial respiratory support for many preterm infants with respiratory distress syndrome (RDS). Nasal intermittent positive-pressure ventilation (NIPPV) seems to increase the beneficial effects of NCPAP by combining it with ventilatory inflations.

This study suggests that NIPPV, as an intial respiratory support for preterm infants with RDS, is feasible and safe and may have beneficial effects, when compared with NCPAP. (Read the full article)

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a progressive, inherited neuromuscular disease manifesting with diaphragmatic paralysis in the first year of life. All patients need mechanical ventilation.

We describe the natural course of SMARD1, developed a scoring system, and defined prognostic values. The clinical outcome of the patients was heterogeneous, and residual enzymatic activity of the IGHMBP2 protein was associated with a more benign disease course. (Read the full article)

Human rhinovirus infections are common in children. Although historically associated with upper respiratory tract illness, rhinoviruses are increasingly recognized for their role in the exacerbation of asthma. Their role in bronchiolitis and severe lung disease in premature infants is unclear.

The authors of this study prospectively explore the role of rhinoviruses in premature infants using molecular techniques and identify these agents as the most frequent cause of hospitalization in this population. (Read the full article)

Upper respiratory tract infections (URIs) are very common in children. Currently, there are no effective preventive measures for URI. There are no studies on the effect of montelukast for prevention of URI.

In a randomized, double-blind, placebo-controlled study of preschool-aged children, 12-week prophylactic treatment with montelukast did not reduce the incidence of URI. (Read the full article)

Nasal continuous positive airway pressure (NCPAP) is a noninvasive ventilatory support that may reduce the need for mechanical ventilation in preterm infants with respiratory distress syndrome. Heliox, a helium-oxygen mixture, has shown positive effects, especially in obstructive diseases.

NCPAP with heliox reduces the need for mechanical ventilation in preterm infants with respiratory distress syndrome in comparison with NCPAP with medical air. (Read the full article)

Although China has the largest birth population in the world and a number of multicenter studies of neonatal respiratory failure are reported, there is a paucity of data regarding outcome measurement of very premature neonates requiring respiratory care and surfactant therapy.

This study is the largest survey, to date, in a Chinese network of 55 NICUs that presents the incidence, morbidity, and mortality rates, with risk factors of neonatal respiratory failure, with special emphasis on surfactant-treated very immature infants. (Read the full article)

Some but not all randomized trials have shown effects of probiotics on incidence and duration of diarrhea and respiratory tract infections among children in developing countries. Calcium improves resistance to intestinal infections in adults, but efficacy in children is unknown.

Lactobacillus reuteri DSM17938 may prevent diarrhea, especially in children with lower nutritional status. Regular calcium milk, alone or with Lactobacillus casei CRL431, did not reduce diarrhea. None of the interventions affected respiratory tract infections in these Indonesian children. (Read the full article)

Rural Alaska children have high rates of hospitalization with lower respiratory tract infections from a variety of pathogens. Past studies of risk factors for respiratory syncytial virus infection associated medically high-risk status, household crowding, and infant feeding practices with hospitalization.

This study reveals the importance of medically high-risk status and infant feeding practices as important factors in respiratory hospitalization. In addition, we identified woodstove use and the absence of 2 or more sinks in household as risk factors for hospitalization. (Read the full article)

Respiratory infectious symptoms are common during the first year of life. Day care attendance, older siblings, and lack of breastfeeding have been considered as possible factors influencing early respiratory tract infections.

Children with early dog contacts seem to have fewer infectious respiratory symptoms and diseases, especially otitis, during the first year of life. (Read the full article)

A growing number of epidemiologic studies suggest that individuals with lower vitamin D levels are at higher risk of acute respiratory tract infection. Randomized controlled trials are needed to determine if vitamin D supplementation would decrease this risk.

In a randomized controlled trial of 247 Mongolian children with vitamin D deficiency in winter, with double-blinding and 99% follow-up, vitamin D supplementation significantly reduced the risk of acute respiratory tract infections. (Read the full article)

Neonatal respiratory distress syndrome is the most common respiratory cause of mortality and morbidity among US infants aged <1 year. Although neonatal respiratory distress syndrome is a heritable disorder, common genetic variants do not fully explain disease heritability.

Single ABCA3 mutations are overrepresented among term and late preterm (≥34 weeks’ gestation) European-descent infants with RDS. Although ABCA3 mutations are individually rare, they are collectively common in the European- and African-descent general population, present in ~4% of individuals. (Read the full article)

Accurately identifying ill hospitalized children with vital signs concerning for clinical deterioration is fundamental to inpatient pediatrics. Normal vital sign ranges for healthy children are useful for outpatient practice but have limited application to detecting deterioration in the hospital setting.

Percentile curves for heart and respiratory rate in hospitalized children were developed and validated. The distributions differed from existing reference ranges and early warning scores. They may be useful to identify vital signs deviating from ranges expected among hospitalized children. (Read the full article)

Heated, humidified high-flow nasal cannula (HHHFNC) is a noninvasive mode of respiratory support that is commonly used in the majority of US NICUs. No large randomized trial has evaluated safety or efficacy of HHHFNC.

This large randomized controlled trial suggests that HHHFNC is as effective as nCPAP for noninvasive respiratory support and can be safely applied to a wide range of neonates. (Read the full article)

Obesity is associated with cardiometabolic risk factors and chronic conditions, such as type 2 diabetes. However, a proportion of overweight and obese youth remain free from cardiometabolic risk factors and are considered metabolically healthy.

This study provides insight into the determinants of cardiometabolic risk factors and the concept in health promotion of "fitness versus fatness." Hepatic lipid accumulation and not fitness level appears to drive cardiometabolic risk factor clustering among overweight and obese youth. (Read the full article)

Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization among infants. Most estimates of RSV hospitalization rates are imprecise, having been calculated by using retrospective discharge diagnosis data and stratified age groups no narrower than 6 to 12 months.

Prospective, population-based surveillance data for infants hospitalized with laboratory-confirmed RSV infection were combined with birth certificate information to yield more precise age-specific hospitalization rates. These data should help determine priorities for the use of existing and future RSV prophylaxis strategies. (Read the full article)

Respiratory support is commonly given to newborn infants via a face mask in the delivery room. Respiratory support given to preterm infants via a single nasal prong may be more effective.

Compared with a face mask, using a single nasal prong to deliver respiratory support to preterm newborns did not result in less intubation and ventilation in the delivery room. (Read the full article)

Preterm birth is associated with increased morbidity during childhood. Many studies have focused on outcomes for preterm births before 32 weeks’ gestation, but there are few follow-up data for late preterm infants (34–36 weeks’ gestation).

The risk of respiratory admission during childhood decreased with each successive week in gestation up to 40 to 42 weeks. The increased risk is small for late preterm infants, but the number affected is large and has an impact on health care services. (Read the full article)

Bacille Calmette-Guerin (BCG) vaccination may provide benefits beyond protecting against pediatric tuberculosis. Evidence suggests links between cell-mediated immunity from tuberculosis and bacterial/viral-related pneumonia but the impact of BCG on acute lower respiratory infection is not fully known.

BCG-vaccinated children had a lower risk of suspected acute lower respiratory infection. Protection was amplified when children were vaccinated against diphtheria-tetanus-pertussis (DTP). Number of DTP doses did not modify this effect, but order in which vaccines were received did. (Read the full article)

Quantitative real-time polymerase chain reaction allows sensitive detection of respiratory viruses. The clinical significance of detection of specific viruses is not fully understood, however, and several viruses have been detected in the respiratory tract of asymptomatic children.

Our results indicate that quantitative real-time polymerase chain reaction is limited at distinguishing acute infection from detection in asymptomatic children for rhinovirus, bocavirus, adenovirus, enterovirus, and coronavirus. (Read the full article)

Down syndrome is an independent risk factor for severe respiratory syncytial virus infection and subsequent hospitalization.

This observational study suggests that immunoprophylaxis may reduce respiratory syncytial virus-related hospitalization by 3.6-fold (95% confidence interval, 1.5–8.7) in children with Down syndrome overall. (Read the full article)

Inadequate nutrient intake can compromise a child’s nutritional status, which may affect immune function. Improving dietary intake via a follow-up formula may support appropriate immune responses and improve a child’s ability to resist infection.

Children who consumed an experimental follow-up formula had fewer episodes and shorter duration of acute respiratory infections, as well as less antibiotic treatment, and fewer days missed of day care due to illness. (Read the full article)

Lower respiratory tract infections (LRTIs), including pneumonia, are in the top 10 causes of death among children in the United States. In high-income countries, 3% to 14% of LRTI hospitalizations have been reported to require admission to an ICU.

During 2007–2011, approximately 31 289 hospitalizations for severe LRTI occurred in children each year in the United States. Children <1 year of age had the highest rates of severe LRTI and accounted for 30% of severe LRTI hospitalizations. (Read the full article)

Many pediatric acute respiratory tract infections (ARTI) are viral and do not require antimicrobial treatment. Recent estimates of antimicrobial overprescribing for these infections, defined based on the published bacterial disease prevalence among all ARTI, are not available.

Based on the published bacterial prevalence rates for pediatric ARTI, antimicrobial agents are prescribed almost twice as often as expected to outpatients nationally, amounting to an estimated 11.4 million potentially preventable antimicrobial prescriptions annually. (Read the full article)

Rhinoviruses are commonly detected in both acutely ill and asymptomatic infants and children. The finding may represent new infection or prolonged presence of rhinovirus RNA in the respiratory tract.

In young, otherwise healthy infants, shedding of RNA from the same rhinovirus strain rarely persisted longer than 30 days. (Read the full article)

Primary ciliary dyskinesia presents in infancy with unexplained neonatal respiratory distress, yet diagnosis is often delayed until late childhood. Earlier diagnosis facilitates earlier onset of therapy, which may help to reduce long-term pulmonary morbidity and mortality.

A diagnostic workup for primary ciliary dyskinesia should be considered in a term infant presenting with unexplained respiratory distress and either lobar collapse, situs inversus, or a prolonged oxygen therapy requirement (>2 days). (Read the full article)

Respiratory syncytial virus (RSV) infection is a common cause of pediatric hospitalizations. Mortality rates associated with RSV hospitalizations are based on estimates from studies conducted decades ago. Accurate understanding of mortality is required for identifying high-risk infants and children.

Mortality associated with RSV is uncommon in the 21st century, with annual deaths far lower than previous estimates. The majority of deaths occurred in infants with complex chronic conditions or in those with life-threatening conditions in addition to RSV infection. (Read the full article)

Making a diagnosis of Kawasaki disease (KD) is often a diagnostic dilemma. This dilemma is confounded when children present with symptoms consistent with known, common respiratory viruses and/or with KD symptoms that could potentially be attributed to a respiratory virus.

Patients with KD commonly have a concurrent respiratory viral infection. Clinicians should not dismiss the diagnosis of KD based on the presence of respiratory symptoms. Furthermore, a positive respiratory virus test result should not be used to exclude the diagnosis of KD. (Read the full article)

Background: This study summarizes drug resistance analyses in 4 recent phase 2b trials of the respiratory syncytial virus (RSV) fusion inhibitor presatovir in naturally infected adults.

Methods: Adult hematopoietic cell transplant (HCT) recipients, lung transplant recipients, or hospitalized patients with naturally acquired, laboratory-confirmed RSV infection were enrolled in 4 randomized, double-blind, placebo-controlled studies with study-specific presatovir dosing. Full-length RSV F sequences amplified from nasal swabs obtained at baseline and postbaseline were analyzed by population sequencing. Substitutions at RSV fusion inhibitor resistance-associated positions are reported.

Results: Genotypic analyses were performed on 233 presatovir-treated and 149 placebo-treated subjects. RSV F variant V127A was present in 8 subjects at baseline. Population sequencing detected treatment-emergent substitutions in 10/89 (11.2%) HCT recipients with upper and 6/29 (20.7%) with lower respiratory tract infection, 1/35 (2.9%) lung transplant recipients, and 1/80 (1.3%) hospitalized patients treated with presatovir; placebo-treated subjects had no emergent resistance-associated substitutions. Subjects with substitutions at resistance-associated positions had smaller decreases in viral load during treatment relative to those without, but similar clinical outcomes.

Conclusions: Subject population type and dosing regimen may have influenced RSV resistance development during presatovir treatment. Subjects with vs without genotypic resistance development had decreased virologic responses but comparable clinical outcomes.

G. C. Liggins
Oct 1, 1972; 50:515-525
ARTICLES

The IMpact-RSV Study Group
Sep 1, 1998; 102:531-537
ARTICLES