Clinical Research Directory

Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES)

The Hyper IgE Syndromes (HIES) are primary immunodeficiencies resulting in eczema and recurrent skin and lung infections. Autosomal dominant Hyper IgE syndrome (AD-HIIES; Job's syndrome) is caused by STAT3 mutations, and is a multi-system disorder with skeletal, vascular, and connective tissue manifestations. Understanding how STAT3 mutations cause these diverse clinical manifestations is critical to our complete understanding of bone metabolism, bronchiectasis, dental maturation, and atherosclerosis. Bi-allelic mutations in DOCK8 cause a combined immunodeficiency previously described as autosomal-recessive Hyper IgE syndrome. These individuals suffer from extensive viral infections as well as have a high incidence of malignancy and mortality. The pathogenesis of this disease and long-term natural history is being investigated. Therefore, we seek to enroll patients and families with a confirmed or suspected diagnosis of HIES syndrome for extensive phenotypic and genotypic study as well as disease management. Patients will be carefully examined by a multidisciplinary team and followed longitudinally. Through these studies we hope to better characterize the clinical presentation of STAT3-mutated HIES, DOCK8 deficiency and other causes of the hyper IgE phenotype, and to be able to identify further genetic etiologies, as well as understand the pathogenesis of HIES. We seek to enroll 300 patients and 300 relatives....

Respiratory Physiotherapy and Inflammatory Biomarkers in Critically Ill Patients With Pneumonia

The goal of this observational study is to evaluate the safety and impact of a protocolized respiratory physiotherapy program on the dynamics of systemic inflammatory biomarkers (procalcitonin \[PCT\] and C-reactive protein \[CRP\]) in critically ill adult patients with pneumonia in the intensive care unit (ICU), compared with standard medical care. The main questions it aims to answer are: Does a protocolized respiratory physiotherapy program accelerate the decline of PCT and CRP levels in critically ill patients with pneumonia compared to standard care? What is the incidence and safety profile of adverse events (e.g., transient desaturation, hemodynamic instability, or mechanical displacement) associated with respiratory physiotherapy sessions? Researchers will compare a prospective cohort receiving structured respiratory physiotherapy against a historical control group receiving standard care to determine changes in inflammatory trajectories and ICU length of stay. Participants in the prospective intervention group will: * Receive an individualized, protocolized respiratory physiotherapy regimen (including high-frequency chest wall oscillation \[HFCWO\], intrapulmonary acoustic percussion, positive expiratory pressure \[PEP\], and/or inspiratory muscle training \[IMT\]) tailored to their clinical deficits. * Undergo continuous safety monitoring during and up to 30 minutes following each physiotherapy session. * Have serum PCT and CRP levels measured at baseline (T0), Day 3 (T1), Day 7 (T2), and at ICU discharge (T3).

Is Osteopathic Manipulative Treatment (OMT) Beneficial for Elderly Patients Hospitalized With Pneumonia?

Osteopathic Manipulative Treatment (OMT) were used in the 1800s and 1900s to treat pneumonia before the introduction of antibiotics in the mid-1900s. The purpose of this study is to determine if OMT, when used in conjunction with antibiotics and other usual care, will improve the recovery of elderly pneumonia patients.

Chest U/S in Differentiating Lung Congestion & Pneumonia in Adult Critically-ill Patients and Its Prognostic Impact

This study aim will be to assess the effectiveness of chest ultrasound as a diagnostic and differentiating modality in cases of pneumonia and lung congestion . It also evaluates chests sonography effectiveness in follow-up of patients with pneumonia and lung congestion .

A Trial of Radial EBUS Versus VBN for the Peripheral Pulmonary Lesions

Peripheral pulmonary lesions are of growing importance in respiratory field. Early detection of lung cancer, tuberculosis and other diseases often needs a bronchoscopic investigation with different types of navigation. Current randomized clinical study is intended to compare three different modalities of navigation in bronchial tree - virtual bronchoscopy (VBN), radial endobronchial ultrasound (EBUS) and combination of both techniques.

Modified Inhaled Nitric Oxide in Ventilated Patients With Acute Respiratory Failure

Pneumonia is the main cause of ICU admission in patients with acute respiratory failure (ARF). Severe pneumonia is a serious lung infection caused by bacteria, fungi, viruses, and other pathogens. It often leads to respiratory failure requiring mechanical ventilation. It is also accompanied by septic shock or multiple organ dysfunction, and patients need intensive care. The average mortality rate is 30%-40%. Therefore, there is an urgent need to find treatments that improve outcomes in patients with severe pneumonia. Inhaled nitric oxide (iNO) can selectively dilate pulmonary vessels in well-ventilated lung areas. This reduces pulmonary artery pressure, improves the ventilation/perfusion ratio, and increases oxygenation. At 80 ppm, iNO can effectively reduce mean pulmonary artery pressure and pulmonary vascular resistance. It also reduces oxidative stress and has anti-inflammatory effects. Short-term inhalation is safe. The level of positive end-expiratory pressure (PEEP) affects the effect of NO. Setting PEEP according to airway opening pressure (AOP) can deliver iNO efficiently to target areas. Based on this, the study team designed this randomized controlled trial to investigate whether a modified iNO regimen, PEEP set according to AOP combined with 80 ppm NO, improves outcomes in patients with acute respiratory failure receiving mechanical ventilation.

Pneumonia and Pleuropneumonia in Hospitalized Children

Describe the epidemiology of hospitalized pediatric pneumonia and pleuropneumonia with pleural effusion: frequency, clinical and biological characteristics, responsible bacteria and pneumococcus place, antibiotic resistance, treatment, vaccine status.

The Effects of Wintergreen Essential Oil Inhalation on Alleviating Dyspnea Among Patients With Pneumonia

Pneumonia is a major public health concern globally and domestically. Dyspnea experienced by hospitalized pneumonia patients often induces anxiety and psychological distress. Wintergreen essential oil, primarily composed of methyl salicylate, is commonly used for comfort care and respiratory relief. This study aims to evaluate the effects of wintergreen essential oil inhalation on dyspnea, physiological parameters, laboratory data, pulmonary function, and subjective comfort in hospitalized pneumonia patients.

Comparative Effectiveness of Readmission Reduction Interventions for Individuals With Sepsis or Pneumonia

An adaptive platform trial to compare effectiveness of different care models to prevent readmissions for patients hospitalized with sepsis or lower respiratory tract infection. The primary outcome is number of days spent at home within 90 days after hospital discharge.

Effects of Lumbrokinase DLBS1033 on D-Dimer, Interleukin-6, and Clinical Outcomes in Patients With Pneumonia and Sepsis

Pneumonia is a lung infection that can cause serious complications, especially when accompanied by sepsis. Sepsis can trigger excessive inflammation and abnormal blood clotting, potentially leading to organ damage and delayed recovery. Two blood markers, D-dimer and interleukin-6 (IL-6), may increase in patients with these conditions. Lumbrokinase DLBS1033 (Disolf®) is an oral treatment derived from the earthworm Lumbricus rubellus. It has properties that may help break down fibrin, a protein involved in blood clot formation, and reduce inflammation. This study aimed to determine whether adding Lumbrokinase DLBS1033 to standard hospital treatment could improve D-dimer and IL-6 levels, shorten the time needed to achieve clinical stability, and reduce the length of hospital stay in patients with pneumonia, sepsis, and hypercoagulability. The study was conducted at Dr. Moewardi General Hospital in Surakarta, Indonesia. A total of 50 hospitalized patients were randomly assigned to two groups of 25 participants each. One group received standard treatment plus oral Lumbrokinase DLBS1033, while the other group received standard treatment plus a placebo containing no active study medicine. Neither the participants nor the blinded study investigators knew which treatment was assigned. Blood samples were collected at three assessment points: baseline (H0), day 10 (H10), and a clinical stability-related assessment designated H+1. D-dimer and IL-6 levels were measured to assess changes in blood clotting activity and inflammation. Participants were also monitored for clinical stability using Halm's Criteria, length of hospital stay, and potential adverse events. The study hypothesis was that Lumbrokinase DLBS1033, when added to standard treatment, would improve D-dimer and IL-6 levels and promote faster clinical recovery compared with standard treatment plus placebo.

Pulmonary-Specific Enteral Nutrition in Mechanically Ventilated Patients With Pneumonia

Pneumonia is a major cause of critical illness and respiratory failure, particularly among patients requiring invasive mechanical ventilation. These patients frequently experience systemic inflammation and metabolic disturbances, which can be assessed using the neutrophil-to-lymphocyte ratio (NLR) and blood lactate levels. Pulmonary-specific enteral nutrition, characterized by a lower carbohydrate and higher fat composition, may help improve respiratory metabolism and modulate inflammatory responses. This double-blind, randomized controlled trial aimed to evaluate the effects of pulmonary-specific enteral nutrition compared with standard enteral nutrition on NLR and blood lactate levels in adult patients with pneumonia requiring invasive mechanical ventilation. Participants were randomly assigned to receive either pulmonary-specific enteral nutrition or standard enteral nutrition. NLR and blood lactate levels were measured on days 1, 3, and 5 to assess changes in inflammatory and metabolic parameters during the intervention period.

Neutrophil Monocyte Lymphocyte Ratios in Pediatric Chest Infections

This prospective cohort study aims to evaluate neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and neutrophil-to-monocyte ratio in children with lobar pneumonia, bronchiolitis, and bronchopneumonia compared with healthy children.

PICNIC Study - PatIent Centered aNtIbiotic Courses in Children With Medical Complexity

To determine if clinicians can safely reduce antibiotic exposure in children with medical complexity (CMC) who are diagnosed with pneumonia by implementing an intervention that bases total antibiotic duration on an individual's clinical stability.

Ketogenic Approach to Restore Muscle in Older Patients With Community-Acquired Pneumonia - KARMA-P Trial

The purpose of the study is to see if a ketogenic diet compared to a standard diet is better to maintain muscle function and health in hospital admitted pneumonia patients.

Comparative Efficacy and Safety of Propofol-Ketamine Combination Versus Propofol Monotherapy in Geriatric Patients Under Invasive Ventilation

The study is a prospective randomized controlled trial comparing the efficacy and safety of propofol-ketamine ("Ketofol") versus propofol monotherapy in geriatric ICU patients. Eligible participants are critically ill elderly patients with a history of cardiac disease who require endotracheal intubation and have not yet received sedation. The investigators focus on a specific population in which geriatric patients have different pharmacokinetics and pharmacodynamics and are more prone to side effects than other populations. Primary outcome: Incidence of hemodynamic instability (defined as hypotension requiring vasopressors), measured by mean arterial pressure (MAP) 5 minutes after induction Secondary outcomes include changes in blood pressure and heart rate, incidence of hypotension, vasopressor requirements, sedation depth, pain scores, cumulative sedative and opioid consumption, adverse events, ICU length of stay, and ICU mortality at predefined intervals.

Study of Lung Proteins in Patients With Pneumonia

This study will examine the different types of proteins present in the lungs of patients with pneumonia to explore the causes of different types of the disease. Pneumonia is a condition that causes lung inflammation AND is often caused by an infection. It is usually diagnosed by lung x-rays and listening to the chest with a stethoscope. This method can diagnose pneumonia, but it does not provide information on the cause of the inflammation - information that might be helpful in guiding treatment. This study will measure proteins in the lungs of patients to see if certain proteins are associated with specific forms of pneumonia, and can thus serve as biomarkers for disease. Patients undergoing diagnostic bronchoscopy at the NIH Clinical Center may participate in this study. Patients will undergo bronchoscopy and bronchoalveolar lavage as scheduled for their medical care. For this procedure, the patient's mouth and throat are numbed with lidocaine; a sedative may be given for comfort. A thin flexible tube called a bronchoscope is advanced through the nose or mouth into the lung airways to examine the airways carefully. Saline (salt water) is then injected through the bronchoscope into the air passage, acting as a rinse. A sample of fluid is then withdrawn for microscopic examination. Researchers in the current study will use some of the fluid obtained from the lavage to examine for protein content. In addition to the bronchoscopy and bronchoalveolar lavage, participants will have about 2 tablespoons of blood drawn to compare blood test results with the results of the lung washings. Patients' medical records will be reviewed to obtain information on past medical history, current medical treatment, vital signs, and results of x-ray tests.

Study of Hospitalised Patients With Acute Respiratory Conditions

The goal of this observational study is to learn about the short- and long-term outcomes of people admitted to hospital with an acute respiratory condition, including exacerbations of chronic lung disease, and to understand factors that may predict recovery, hospital readmission, length of hospital stay, and mortality. A group of people with chronic respiratory disease who are being followed in respiratory outpatient clinics and a healthy control group without lung disease will also take part. The main questions it aims to answer are: * Which clinical, physical, functional, and biological characteristics are associated with short-term outcomes after hospitalisation, including 30-day hospital readmission, length of hospital stay, and 30-day mortality? * Which characteristics are associated with longer-term recovery, future exacerbations, hospital readmissions, healthcare use, and mortality? * Can measurements taken during or around the time of hospitalisation be used to identify people at greater risk of poor outcomes who may benefit from targeted interventions? Participants will undergo clinical assessments that may include questionnaires, measurements of physical function and muscle strength, lung function tests, physical activity monitoring, and collection of biological samples. Some participants may also undergo additional assessments of body composition, muscle size and function, imaging, or muscle metabolism, including through nested sub-studies. Participants will be followed for up to 36 months to assess recovery and longer-term clinical outcomes.

Novel Tools to Improve Management of Paediatric Community-Acquired Pneumonia - ToolCAP

The ToolCAP study aims to see if using ultrasound to look at the lungs when children have symptoms of a lung infection will safely allow doctors to improve how they treat those infections. The study will also look at if it's possible to improve how doctors decide which children need antibiotics. * Lung infections are the most common reason for children to go to the clinic/hospital. * Doctors usually give an antibiotic to every child with a lung infection. * Lung infections can be caused by 2 different types of germs - bacteria or viruses. * Antibiotics only work against bacteria and not against viruses. Lung infections caused by viruses don't need antibiotics as the body fights them by itself. * Lots of research now shows that only 1 in 4 children with a lung infection actually needs an antibiotic, as the rest only have a viral infection causing the symptoms. * This means that 3 in 4 children get an antibiotic when they don't need it. * Taking too many antibiotics can cause problems for children as it can cause diseases like diabetes or asthma. * Nowadays, due to too many people using too many antibiotics, experts are starting to worry that bacteria are starting to become resistant (stronger than the antibiotic). * Ultrasound of the lungs appears to be a way of safely looking at the lungs to see if there is an infection and may help doctors better decide who needs an antibiotic. This study includes children aged 2 months-12 years who come to the hospital with a lung infection. Children who are very unwell or who have already had 2 days of antibiotic treatment will not be allowed to be in the study.

Inhaled Lexofloxacin vs Usual Care for Treatment of Community-Acquired Pneumonia

This trial aims to determine whether treatment with inhaled levofloxacin (an antibiotic) is equal to systemic antibiotic treatment (usual care) for patients admitted to a hospital with community-acquired pneumonia in regards to treatment-effect and safety parameters. Additionally, this study will assess if treatment with inhaled antibiotics leads to fewer antibiotic side-effects and a more preserved gastro-intestinal microbial environment. The main question this study aims to answer is: Does inhaled levofloxacin 240mg twice daily result in comparable days alive and out of hospital at 14 days compared to standard-of-care (usual care) antibiotic treatment for community-acquired pneumonia in admitted patients? Secondary questions this study aims to answer are: 1. Does treatment with inhaled levofloxacin reduce proportion of patients with antibiotic side-effects? 2. Does treatment with inhaled levofloxacin lead to preserved diversity in the gut microbiome? 3. Is treatment with inhaled levofloxacin comparable with usual care in regards to patient reported outcomes? The above list is not the complete list of questions this study aims to answer, but serves as highlights.

Phase 2a Multiple Ascending Dose Study in Hospitalized Patients With Pneumonia.

A Phase 2a, randomized, double-blind, placebo-controlled, multiple ascending dose study in patients who are hospitalized with presumed pneumonia requiring supplemental oxygen therapy. The purpose of this study is to examine the safety, tolerability and efficacy of AV-001 Injection administration daily to the earlier of day 28 or EOT (day prior to hospital discharge). A total of 60 eligible patients (20 patients in each of cohort 1, 2 and 3) will be recruited from up to 25 participating institutions/hospitals. Patients will be randomized in a 1:1 ratio to receive either AV-001 Injection or AV-001 placebo Injection, together with standard of care (SOC).

Effect of Pursed-Lip Breathing on Physiological Parameters and Discharge Readiness in Children With Pneumonia

This study aims to evaluate the effects of Pursed-Lip Breathing (PLB) exercises on physiological parameters (such as respiratory rate, heart rate, and oxygen saturation) and discharge readiness in children diagnosed with pneumonia. The study is designed as a randomized controlled trial involving pediatric patients between the ages of 3 and 4. The intervention includes guided PLB exercises performed twice daily for three consecutive days. Data will be collected before and after each session to assess changes in physiological measures and readiness for hospital discharge.

Optimising Antibiotic Use for Paediatric Lower Respiratory Tract Infections in Africa

Lower respiratory tract infections (LRTIs) remain a leading cause of hospitalisation and death among young children in Africa. Although viral infections account for a substantial proportion of LRTIs, antibiotics are frequently prescribed because distinguishing between viral and bacterial infections can be challenging. This contributes to unnecessary antibiotic exposure and the rising global public health challenge of antimicrobial resistance. This pragmatic, unblinded randomised controlled study will evaluate whether the combination of point-of-care (POC) C-reactive protein (CRP) testing and the PREPARE clinical severity score can safely reduce antibiotic use among children aged 2 to 24 months hospitalised with LRTI at Chris Hani Baragwanath Academic Hospital (CHBAH), South Africa. Participants will be randomly assigned in a 1:1 ratio to either the intervention group, where antibiotic decisions are guided by serial POC CRP measurements and repeated PREPARE severity assessments, or a control group receiving routine clinical care. The primary objective of the study is to compare antibiotic use during hospitalisation between the intervention and control groups. Secondary objectives are to evaluate the safety of this approach by comparing mortality, hospital readmission within 28 days, adverse events, need for invasive ventilation, duration of hospitalisation, and other clinical outcomes between study groups. In addition, the study will compare healthcare-related costs, including antibiotic expenditure and costs associated with hospitalisation. A parallel mixed-methods component will explore clinician attitudes, beliefs, and determinants of antibiotic prescribing for children hospitalised with LRTI using surveys, focus groups discussions, and individual interviews informed by the Theoretical Domains Framework (TDF). Findings will help identify behavioural and system-level factors that influence antibiotic prescribing and inform future antimicrobial stewardship interventions. This study aims to generate evidence on whether biomarker-guided and risk-stratified care can safely optimise antibiotic use among young African children hospitalised with LRTI while improving antimicrobial stewardship and reducing healthcare costs.

The LalelaLung Study: Digital Stethoscope Clinical Evaluation

Pneumonia is the leading infectious cause of death in children under five years of age worldwide, and most of these deaths occur in low- and middle-income countries. In these settings, frontline health workers diagnose pneumonia using the World Health Organization's Integrated Management of Childhood Illness (IMCI) guidelines, which rely mainly on counting how fast a child is breathing and checking for chest indrawing. This approach has saved many lives, but it is not very specific. As a result, many children who actually have self-limiting viral illnesses that do not require antibiotics are nonetheless treated with antibiotics, contributing to the global rise of antimicrobial resistance. New digital stethoscopes paired with artificial intelligence (AI) can record a child's lung sounds and automatically detect abnormal sounds such as crackles and wheezes with accuracy comparable to physicians. The LaLeLa Lung Study will evaluate whether adding an AI-enabled digital stethoscope to standard IMCI assessment improves the accuracy of pneumonia diagnosis among children aged 2 to 59 months who present with cough and/or difficult breathing at a primary care clinic in Cape Town, South Africa. The main component (Objective 1) is a randomized, triple-blinded diagnostic accuracy study that will enroll 350 children, randomly assigned in a 1:1 ratio to either IMCI care enhanced by the AI-enabled digital stethoscope or standard IMCI care. An independent panel of physicians, blinded to the AI results and to study-arm assignment, will review each case and serve as the reference standard for determining whether pneumonia was truly present. The investigators hypothesize that IMCI enhanced by the AI stethoscope will diagnose pneumonia more accurately, and target antibiotics more appropriately, than standard IMCI alone. Nested sub-studies will additionally evaluate a second AI stethoscope for tuberculosis detection, a wearable lung-sound and respiratory-rate patch, an automated respiratory-rate monitor, and a smartphone-connected pulse oximeter. A separate component (Objective 2) is a mixed-methods implementation study at a second clinic that will assess how easily health workers can use these devices, how acceptable the devices are to health workers and caregivers, and how well the devices fit into routine clinic workflows. Throughout the study, all AI-generated results will remain concealed from clinic staff, study clinicians, and caregivers, so the AI-generated results will not influence the care any child receives. All children continue to receive standard IMCI care. Findings will help inform whether AI-enabled digital auscultation should be integrated into childhood pneumonia care in South Africa and similar low-resource settings, with the goal of improving diagnosis, strengthening antibiotic stewardship, and reducing antimicrobial resistance and child mortality.

Validation and Clinical Utility of the Lung Sliding Index (LSI) for Differentiating Pulmonary Diseases

This upcoming case-control study aims to confirm the Lung Sliding Index (LSI), a new ultrasound score that measures how well the pleura moves, in various lung diseases. The study will check how well the LSI can tell apart different lung diseases (like pneumothorax, interstitial lung disease, COPD, pneumonia, and pulmonary edema), how it relates to signs of disease severity, and how consistent the results are between different operators who have received the same training. Secondary objectives include assessing patient and operator satisfaction and feasibility using validated Likert scales.