DeCure's autonomous Respiratory AI scientist is researching a drug-repurposing hypothesis for bronchitis — screening already-approved drugs against its 14-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBronchitis maps to a 14-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
approvedRoflumilastPhosphodiesterase 4 inhibitor
Structures already discussed alongside bronchitis in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Catalytic Domain Of Human Phosphodiesterase 4D — Roflumilast has a real, experimentally solved structure in complex with this target (PDB 1XOQ, 1.83 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 rofdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1XOQ · 1.83 Å · ligand Roflumilast (ROF). Experimental structure, not a prediction.
What the evidence adds up to
In the RE(2)SPOND trial, 2,354 participants with severe or very severe COPD, chronic bronchitis, and a history of exacerbations were given either roflumilast 500 µg daily or placebo on top of inhaled corticosteroid/long-acting β2-agonist with or without a long-acting muscarinic antagonist. The rate of moderate or severe exacerbations per patient per year was reduced by 8.5% with roflumilast, but the difference was not statistically significant (rate ratio 0.92; 95% CI 0.81–1.04; P = 0.163). Lung function did improve. In a post hoc analysis of participants with more than three exacerbations or at least one hospitalisation in the prior year, the reduction became significant. Adverse event-related discontinuations were 11.7% on roflumilast versus 5.4% on placebo; deaths were 2.5% versus 2.1%. A 2018 cost-effectiveness analysis using REACT and RE(2)SPOND data found that roflumilast added to triple inhaled therapy produced non-significant reductions in moderate and severe exacerbations overall, with an incremental cost-effectiveness ratio of £24,976. In patients with a prior COPD-related hospitalisation, the reduction in severe exacerbations was statistically significant, and the ICER fell to £7,087.
Two older trials examined antibiotics for exacerbations of chronic bronchitis. In a 1969 single-blind trial of 50 patients, trimethoprim 320 mg plus sulphamethoxazole 1,600 mg daily was compared with ampicillin 2 g daily. The combination was judged more effective by clinical response and by reduction in sputum volume and purulence, with eradication of pathogenic organisms. No appreciable side-effects were reported. A 1979 single-blind trial of 56 patients compared trimethoprim/sulphamethoxazole with doxycycline for one week and found no significant difference in response; both were described as effective and well tolerated.
A 2025 study of 126 paediatric patients with post-infectious bronchiolitis/bronchitis obliterans identified twelve variants of the DNAH9 gene in six children. Three had bronchiolitis obliterans, two had bronchitis obliterans, and one had both. All had at least one prior pneumonia episode: three linked to Mycoplasma pneumoniae, two to adenovirus, and one to co-infection. The variants included two nonsense mutations, two near splice sites, and eight missense mutations; all were classified as variants of uncertain significance or predicted deleterious by bioinformatics, with negligible or low minor allele frequencies. The authors suggest DNAH9 compound complex variants may contribute to PIBO after severe M. pneumoniae or adenoviral pneumonia.
Two 2023 articles discuss bronchitis classification and treatment in general terms. One presents a classification project and a schematic diagram of etiological and pathogenetic treatment, noting a large proportion of viral and related infections at the Lamb stage. The other states that bronchitis in children under one year requires qualified medical advice, that different forms need specific treatment, and that hospital treatment is recommended for obstructive bronchitis and bronchiolitis. Neither provides new trial data or quantitative 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.
American Journal of Respiratory and Critical Care Medicine · 2016 · 127 citations
Effect of Roflumilast and Inhaled Corticosteroid/Long-Acting β2-Agonist on Chronic Obstructive Pulmonary Disease Exacerbations (RE2SPOND): A Randomized Clinical Trial
AbstractRATIONALE: Moderate and severe exacerbations are incompletely prevented by maximal inhalation therapy in patients with severe chronic obstructive pulmonary disease. OBJECTIVES: To determine whether roflumilast reduces moderate and/or severe chronic obstructive pulmonary disease exacerbations in patients at risk for exacerbations despite treatment with inhaled corticosteroid/long-acting β2-agonist with or without a long-acting muscarinic antagonist (LAMA). METHODS: In this 52-week, phase 4, double-blind, placebo-controlled RE(2)SPOND (Roflumilast Effect on Exacerbations in Patients on Dual [LABA/ICS] Therapy) trial (NCT01443845), participants aged 40 years or older with severe/very severe chronic obstructive pulmonary disease, chronic bronchitis, two or more exacerbations and/or hospitalizations in the previous year, and receiving inhaled corticosteroid/long-acting β2-agonist with or without LAMA daily for 3 or more months were equally randomized to once-daily roflumilast, 500 μg (n = 1,178), or placebo (n = 1,176). Stratification was based on LAMA use. MEASUREMENTS AND MAIN RESULTS: Although rate of moderate or severe exacerbations per patient per year (primary endpoint) was reduced by 8.5% with roflumilast versus placebo, the between-group difference was not statistically significant (rate ratio, 0.92; 95% confidence interval, 0.81-1.04; P = 0.163). However, roflumilast improved lung function, and in a post hoc analysis roflumilast significantly reduced the rate of moderate or severe exacerbations in participants with a history of more than three exacerbations and/or one or more hospitalizations in the prior year. Adverse event-related discontinuations occurred in 11.7% roflumilast-treated and 5.4% placebo-treated participants. Deaths occurred in 2.5% roflumilast and 2.1% placebo participants. CONCLUSIONS: Roflumilast failed to statistically significantly reduce moderate and/or severe exacerbations in the overall population. Roflumilast improved lung function and reduced exacerbations in participants with frequent exacerbations and/or hospitalization history. The safety profile of roflumilast was consistent with that of previous studies. Clinical trial registered with www.clinicaltrials.gov (NCT01443845).
Single-blind comparative trial of trimethoprim-sulphamethoxazole and ampicillin in the treatment of exacerbations of chronic bronchitis
AbstractFifty patients with exacerbations of chronic bronchitis were treated with either a combination of trimethoprim 320 mg. and sulphamethoxazole 1,600 mg. a day or ampicillin 2 g. a day. The trial, carried out as a single-blind procedure, showed that the combination was more effective as judged by clinical response and reduction in sputum volume and purulence, with eradication of pathogenic organisms. No appreciable side-effects were encountered with either treatment, and it is suggested that the trimethoprim-sulphamethoxazole combination may be a safe and useful drug in the treatment of chronic bronchitis.
International Journal of COPD · 2018 · 8 citations · open access
Cost-effectiveness of roflumilast as an add-on to triple inhaled therapy versus triple inhaled therapy in patients with severe and very severe COPD associated with chronic bronchitis in the UK
AbstractPurpose: Patients with severe COPD are at high risk of experiencing disease exacerbations, which require additional treatment and are associated with elevated mortality and increased risk of future exacerbations. Some patients continue to experience exacerbations despite receiving triple inhaled therapy (ICS plus LAMA plus LABA). Roflumilast is recommended by the Global Initiative for Chronic Obstructive Lung Disease as add-on treatment to triple inhaled therapy for these patients. This cost-effectiveness analysis compared costs and quality-adjusted life-years for roflumilast plus triple inhaled therapy vs triple inhaled therapy alone, using data from the REACT and RE 2 SPOND trials. Patients and methods: Patients included in the analysis had severe to very severe COPD, FEV 1 <50% predicted, symptoms of chronic bronchitis and ≥2 exacerbations per year. Our model was adapted from a previously published and validated model, and the analyses conducted from a UK National Health Service perspective. A scenario analysis considered a subset of patients who had experienced at least one COPD-related hospitalization within the previous year. Results: Roflumilast as add-on to triple inhaled therapy was associated with non-significant reductions in rates of both moderate and severe exacerbations compared with triple inhaled therapy alone. The incremental cost-effectiveness ratio (ICER) for roflumilast as add-on to triple inhaled therapy was £24,976. In patients who had experienced previous hospitalization, roflumilast was associated with a non-significant reduction in the rate of moderate exacerbations, and a statistically significant reduction in the rate of severe exacerbations. The ICER for roflumilast in this population was £7,087. Conclusions: Roflumilast is a cost-effective treatment option for patients with severe or very severe COPD, chronic bronchitis, and a history of exacerbations. The availability of roflumilast as add-on treatment addresses an important unmet need in this patient population. Keywords: National Health Service, National Institute for Health and Care Excellence, exacerbation rates
The Medical Journal of Australia · 1979 · 4 citations
TRIMETHOPRIM/SULPHAMETHOXAZOLE AND DOXYCYCLINE IN ACUTE EXACERBATIONS OF CHRONIC BRONCHITIS IN GENERAL PRACTICE: A COMPARATIVE STUDY
AbstractFifty-six patients with acute exacerbation of chronic bronchitis were given one week's treatment either with a combination of trimethoprim and sulphamethoxazole (TMP/SMX) or with doxycycline, in a single blind trial. The study found no significant difference in response to the two treatments, and confirmed that both TMP/SMX and doxycycline are effective and well tolerated agents, which are suitable for the management of acute or chronic bronchitis.
Orphanet Journal of Rare Diseases · 2025 · 4 citations · open access
DNAH9 variants in children with post-infectious bronchiolitis/bronchitis obliterans
AbstractPost-infectious bronchiolitis/bronchitis obliterans (PIBO) is a chronic irreversible obstructive lung disease that results in obstruction and/or obliteration of small airways. Previous reports have indicated that PCD-related gene mutations contribute to PIBO incidence. However, the relationship between DNAH9 variants and PIBO remains unclear. This study aimed to evaluate the association between DNAH9 mutations and the incidence of PIBO. In our cohort, 126 PIBO patients conducted Whole Exome Sequence (WES) test and twelve variants of DNAH9 gene were identified. Detailed clinical information, high-resolution computerized tomography and/or electronic bronchoscopy findings of the six pediatric children carried DNAH9 variants were systematically collected, meticulously reviewed, and rigorously analyzed. Clinical evaluation revealed three patients with bronchiolitis obliterans, two patients with bronchitis obliterans and one with both conditions. All patients had at least one previous bout of pneumonia, which in three cases was linked to Mycoplasma pneumoniae, in two cases to adenovirus infection, and in one case to co-infection with both pathogens. Genetic analysis of all cases identified six compound heterozygous DNAH9 mutations encompassing twelve variants: c.12,925 C > T (p.Arg4309*), c.5152-10G > T (-), c.4604 A > G (p.Gln1535Arg), c.12844-14T > C (-), c.4816T > C (p.Phe1606Leu), c.8831G > A (p.Arg2944Gln), c.9479 C > T (p.Ala3160Val), c.7415G > A (p.Arg2472Gln), c.5692G > T (p.Glu1898*), c.11,572 C > T (p.Arg3858Trp), c.11,176 C > T (p.Arg3726Trp), c.1010 C > T (p.Pro337Leu). These variants included two nonsense mutations, two mutations near splice sites, and eight missense mutations. All variants exhibited negligible or low minor allele frequencies based on the gnomAD database and were predicted to be variants of uncertain significance (VUS) or deleterious based on comprehensive bioinformatics analysis. Our findings suggest that DNAH9 compound complex variants may contribute to development of PIBO following severe M. pneumoniae and/or adenoviral infectious pneumonia in pediatric patients.
Zenodo (CERN European Organization for Nuclear Research) · 2023 · 0 citations · open access
CLASSIFICATION, CLINIC, DIAGNOSIS AND CLAIM PRINCIPLES OF ETIOPATHOGENESIS ACCORDING TO THE FORM OF BRONCHITIS
Abstract<em>On this basis, a classification project was presented in terms of finding realistic approaches to primary prevention of features of chronic bronchitis stages. At the Lamb stage of this disease, a large proportion of viral and related infections have been identified. A schematic diagram of etiological and patho-genetic treatment is presented. In this article we can discuss information about classification, clinic, diagnosis and claim principles of etiopathogenesis according to form of bronchitis.</em>
Профилактическая медицина и здоровье · 2023 · 0 citations · open access
Bronchitis in children under one year of age and methods of its treatment
AbstractIn this article, treatment of Bronchitis is a long and difficult process. In any case, the recommendations of a qualified doctor are necessary, because different forms of the disease require the use of specific treatment methods. Treatment procedures are different: etiotropic - elimination of the causative factor (virus or bacteria), symptomatic treatment - elimination of life-threatening symptoms, in case of obstructive bronchitis and bronchiolitis, hospital treatment is recommended.
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.
