DeCure for Bronchiectasis with or without elevated sweat chloride 1
DeCure's autonomous Respiratory AI scientist is researching a drug-repurposing hypothesis for bronchiectasis with or without elevated sweat chloride 1 — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBronchiectasis with or without elevated sweat chloride 1 maps to a 3-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
approvedIvacaftorApproved drug
Structures already discussed alongside bronchiectasis with or without elevated sweat chloride 1 in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
The complex of phosphorylated human delta F508 cystic fibrosis transmembrane conductance regulator (CFTR) — Ivacaftor has a real, experimentally solved structure in complex with this target (PDB 8EIQ, 3.0 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet vx7drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8EIQ · 3.0 Å · ligand Ivacaftor (VX7). Experimental structure, not a prediction.
What the evidence adds up to
In 1959, sweat chloride was measured in 96 subjects assumed free of cystic fibrosis and never exceeded 70 mEq per litre; in 6 patients with cystic fibrosis it always exceeded 75 mEq per litre. Among 25 patients with cylindrical bronchiectasis, 8 had abnormal values of 69 mEq per litre of chloride or 79 or more mEq per litre of sodium. The authors concluded that cystic fibrosis should be considered among possible causes of chronic endobronchial disease.
A 2003 case report described an 18-year-old female with bronchiectasis, chronic P. aeruginosa infection, and normal sweat chloride concentrations who experienced rapid decrease of lung function and clinical deterioration despite treatment. Broad genotyping showed compound heterozygosity with deltaF508 and 3849+10 kb C-->T mutations, confirming cystic fibrosis. The authors stated that alternative diagnostic tests such as genotyping and electrophysiologic measurements must be performed if there is suspicion of cystic fibrosis despite normal or borderline sweat chloride levels.
A 2025 case report described a 50-year-old female with long-standing bronchiectasis and recurrent exacerbations whose initial sweat chloride testing yielded 21 and 28 on two separate occasions. Genetic testing revealed G551D and D1152H mutations, variants known to be associated with normal sweat chloride. The patient responded positively to combination therapy with Elexacaftor, Tezacaftor and Ivacaftor, which is indicated for her genotype. The authors noted that variants like D1152H have been reported with normal sweat chloride levels and that the patient's improvement on CFTR modulator therapy further supports genotype-driven treatment strategies.
What is still missing is prospective data on how many bronchiectasis patients with normal sweat chloride harbour CFTR mutations, standardised criteria for when to proceed to genotyping in this population, and trials that stratify such patients by genotype before assigning modulator therapy. The evidence remains limited to case reports and small series; no controlled trial has tested whether routine genotyping in bronchiectasis with normal sweat chloride improves outcomes.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
JAMA · 1959 · 57 citations
CONSIDERATION OF CYSTIC FIBROSIS IN ADULTS, WITH A STUDY OF SWEAT ELECTROLYTE VALUES
AbstractThe sweat test used in the diagnosis of cystic fibrosis consists of the determination of chloride and sodium concentrations. In this study the sweat was collected on small cellulose sponges sealed against certain cleansed areas of skin. The test was applied to 34 persons a total of 89 times to determine its reliability. In 96 subjects assumed to be free from all known forms of cystic fibrosis, the chloride content of sweat never exceeded 70 mEq. per liter; in 6 patients with cystic fibrosis it always exceeded 75 mEq. per liter. Abnormal values of 69 mEq. per liter of chloride or 79 or more mEq. per liter of sodium were found in 8 of 25 patients with cylindrical bronchiectasis. Evidence indicates that cystic fibrosis is a general dysfunction of exocrine glands and that it should be considered among the possible causes of chronic endobronchial disease.
Revista do Hospital das Clínicas · 2003 · 11 citations · open access
Cystic fibrosis with normal sweat chloride concentration: case report
AbstractCystic fibrosis is a genetic disease usually diagnosed by abnormal sweat testing. We report a case of an 18-year-old female with bronchiectasis, chronic P. aeruginosa infection, and normal sweat chloride concentrations who experienced rapid decrease of lung function and clinical deterioration despite treatment. Given the high suspicion of cystic fibrosis, broad genotyping testing was performed, showing a compound heterozygous with deltaF508 and 3849+10 kb C-->T mutations, therefore confirming cystic fibrosis diagnosis. Although the sweat chloride test remains the gold standard for the diagnosis of cystic fibrosis, alternative diagnostic tests such as genotyping and electrophysiologic measurements must be performed if there is suspicion of cystic fibrosis, despite normal or borderline sweat chloride levels.
American Journal of Respiratory and Critical Care Medicine · 2025 · 0 citations
Breaking the Mold: A Case of Cystic Fibrosis Beyond Sweat Chloride
AbstractAbstract Introduction: Cystic Fibrosis (CF) is traditionally diagnosed through elevated sweat chloride levels followed by genetic testing. However, depending on types of specific CFTR gene mutations, sweat chloride test may not always be conclusive. This case study presents a unique instance of CF in a 50-year-old patient with negative sweat chloride levels who was later found to have CFTR dysfunction during the evaluation for worsening bronchiectasis, highlighting the diagnostic challenges posed by atypical presentations. Description: A 50-year-old female with a long-standing history of bronchiectasis and recurrent exacerbations was evaluated at our clinic. Initial sweat chloride testing yielded negative results (21 and 28 on two separate occasions), which made a CF diagnosis very unlikely. She was subsequently treated with standard airway hygiene measures while alternative diagnoses were explored. However, despite thorough work-up and management, her bronchiectasis continued to worsen, leading to genetic testing to complete the comprehensive evaluation of her condition. The CFTR mutation panel revealed the presence of G551D and D1152H (variants known to be associated with normal sweat chloride test). Despite the negative sweat chloride test, the patient's clinical presentation, including bronchiectasis, recurrent exacerbations, and the identified CFTR mutations, supported a diagnosis of CF. The patient has since responded positively to combination therapy with Elexacaftor, Tezacaftor and Ivacaftor, which is indicated for her genotype. Discussion: This case underscores the limitations of relying solely on sweat chloride testing for diagnosing CF, particularly in patients with atypical CFTR mutations. Variants like D1152H have been reported with normal sweat chloride levels, challenging traditional diagnostic paradigms. Genetic testing plays a crucial role in these cases by identifying mutations that may still lead to significant CFTR dysfunction. The patient's improvement on CFTR modulator therapy further supports the role of genotype-driven treatment strategies in CF care. This case highlights the need for a broader diagnostic approach, including comprehensive genetic testing and clinical correlation, especially for patients presenting with non-classical CF features. It contributes to the growing understanding that CF is a spectrum disorder with varied clinical and biochemical presentations, emphasizing the importance of individualized diagnosis and treatment strategies to optimize patient outcomes.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
