Association of pruritus and chronic cough: an all of us database study

Abstract

Purpose

Based on a potential shared pathophysiology tied to mast cell activity and neurogenic inflammation that may link pruritus and chronic cough (CC), this study, leveraging the All of Us database, examines the association between the two conditions.

Materials and methods

A nested case-control comparison was used to examine the association, identifying cases with SNOMED codes 418363000 (pruritus) and 68154008 (CC). Matching was performed on a 1:4 ratio by age, sex, and ethnicity using the MatchIt package in R, followed by maximum likelihood method to estimate odds ratios (ORs) and 95% confidence intervals from 2x2 contingency tables.

Results

CC patients (n = 2,388) were more than twice as likely to be diagnosed with pruritus (OR: 2.65) and pruritus patients (n = 22,496) were more than twice as likely to be diagnosed with CC (OR: 2.57), than respective matched controls.

Conclusions

These results highlight the potential bidirectional relationship between CC and pruritus, suggesting possible shared immune and neural pathways. Treatments like difelikefalin and nalbuphine that modulate these pathways, alongside P2X3 targeting agents, are emerging as potential therapeutic approaches for itch and chronic cough given the possible interconnected pathophysiology. This study’s insights into the associations between pruritus and CC may pave the way for targeted therapeutic strategies that address their shared mechanisms.

Keywords:

• Chronic cough
• itch
• pruritus
• mast cell dysfunction
• central sensitization

Disclosure statement

BU is an employee of Mount Sinai and has received research funds (grants paid to the institution) from: Incyte, Rapt Therapeutics, and Pfizer. He is also a consultant for Arcutis Biotherapeutics, Bristol Myers Squib, Castle Biosciences, Fresenius Kabi, Galderma, Janssen, Lilly, Pfizer, Primus Pharmaceuticals, Sanofi, and UCB. BSK is an employee of Mount Sinai. He also has received personal fees from Abbvie, Agenx, Abrax, Japan, Almirall, S.A., Amagma, Amgen, Bristol-Myers Squibb, Cara Therapeutics, Eli Lilly and Company, Evommune, Escient Pharmaceuticals, Galderma S.A., Glaxo­SmithKline, Genzyme, Granular Therapeutics, Guidepoint Global, Incyte Corporation, Janssen Pharmaceuticals, Inc., LEO Pharma,Pfizer Inc., Novartis, Recens, Regeneron, Medical,Trevi Therapeutics. JCDR is an employee of Mount Sinai. The rest of the authors declare no relevant conflicts of interest.

Data availability statement

Access to the Researcher Workbench and data is free. All researchers must be authorized and approved via a 3-step process that includes registration, completion of ethics training and attestation to a data use agreement.

Additional information

Funding

The All of Us Research Program is supported by the National Institutes of Health, Office of the Director: Regional Medical Centers: 1 OT2 OD026549; 1 OT2 OD026554; 1 OT2 OD026557; 1 OT2 OD026556; 1 OT2 OD026550; 1 OT2 OD 026552; 1 OT2 OD026553; 1 OT2 OD026548; 1 OT2 OD026551; 1 OT2 OD026555; IAA #: AOD 16037; Federally Qualified Health Centers: HHSN 263201600085U; Data and Research Center: 5 U2C OD023196; Biobank: 1 U24 OD023121; The Participant Center: U24 OD023176; Participant Technology Systems Center: 1 U24 OD023163; Communications and Engagement: 3 OT2 OD023205; 3 OT2 OD023206; and Community Partners: 1 OT2 OD025277; 3 OT2 OD025315; 1 OT2 OD025337; 1 OT2 OD025276. In addition, the All of Us Research Program would not be possible without the partnership of its participants.