DataSheet1_Efficacy and safety of combination therapy with pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis.docx

Background: Recent studies have suggested that combination therapy with pirfenidone and nintedanib is safe and tolerable in patients with idiopathic pulmonary fibrosis (IPF). However, data from real-world practice are limited. Thus, we aimed to investigate the safety and efficacy of this combination therapy in patients with IPF in a real-world setting.Methods: A multicenter retrospective cohort study was conducted to investigate the safety and efficacy of combination therapy with pirfenidone and nintedanib in 45 patients with IPF. Incidences of adverse events and rates of lung function decline were compared before and after the combination therapy. Propensity score matching was performed to compare the outcomes between the combination and monotherapy groups.Results: The mean age of the patients was 68.8 years, and 82.2% of them were male. The median follow-up duration after combination therapy was 12.1 months. The majority of the patients (97.8%) received nintedanib as an add-on to pirfenidone. The most common adverse events after the combination therapy were diarrhea and anorexia. Pirfenidone or nintedanib was stopped in 12 patients owing to gastrointestinal AEs, lung transplantation, or financial problems. In patients with serial lung function data, the rate of decline in the forced vital capacity was significantly reduced after the combination therapy. In the matched analysis, the combination group had a higher incidence of diarrhea than the monotherapy group without an increase in serious adverse events; however, the two groups had similar changes in forced vital capacity (FVC).Conclusion: The combination of pirfenidone and nintedanib in patients with IPF has the potential to reduce the rate of FVC decline. However, in the matched analysis, FVC decline was comparable between the patients on combination therapy and those on monotherapy. The incidence of certain adverse events, particularly diarrhea, was higher with combination therapy, but serious adverse events were similar between the groups.</p

Thermostability of Ap-contained oligo-microsphere.

<p>Thermostability of Ap-contained oligo-microsphere.</p

DNA presentation and fluorescence image of probe binding to the surface of 3-D microsphere.

<p>(A) The fluorescent signal demonstrated that the oligonucleotides (5’<u>A</u>crydite-modified DNA <u>p</u>robe, Ap) on the surface of the microsphere were capable of hybridizing to the complementary fluorescent labeled DNA probes. (B) The complementary binding performance was visible only on the surface area of Ap-contained microsphere. (C) Z-stack fluorescence images of a single microsphere captured with 3D confocal fluorescence microscopy at different Z-planes. Non-specific interaction or absorption of complementary DNA probes to any of the inside area was not observed in Z-stack fluorescent images. Images were collected at 7.6 <b>μ</b>m intervals using a 488 laser.</p

A graphical summary of the Microsphere-PCR protocol.

<p>The Microsphere-PCR synthesizes ssDNA copy of a DNA template.</p

Fabricated polymeric droplet-based microfluidic platform and on-flow microsphere synthesis.

<p>(A) Droplet-based microfluidic platform, (B) Flow-focusing geometry. (C) Overall experimental set-up for producing polyacrylamide microspheres. (D) On-flow synthesis of polyacrylamide microsphere in the main channel. The inset figure shows the ccaptured image being formed microspheres.</p

Microsphere-PCR for amplifying ssDNA.

<p>(A) The DNA amplicons were run on a 2% agarose gel followed by EtBr staining. (B) Agarose gel configuration to determine the relative location of PCR bands and their intensity from asymmetric PCR and microsphere-PCR experiments. M: Synthesized ssDNA Marker (76 nt, 100 nt), Lane 1: Asymmetric PCR (primer (F/R) ratio_20: 1), Lane 2: Microshperes-PCR. (C) Melting Tm analysis for synthetic DNA hybrids (Reference Duplex, RD) and Microsphere-PCR dsDNA byproducts. Co-polymerized Ap-microspheres was tested as a control. (ND: Not detected).</p

Sequences of oligonucleotides used to amplify ssDNA based on microsphere-PCR.

<p>Sequences of oligonucleotides used to amplify ssDNA based on microsphere-PCR.</p

sj-docx-1-tar-10.1177_17534666231169472 – Supplemental material for Heterogeneity of asthma–chronic obstructive pulmonary disease (COPD) overlap from a cohort of patients with severe asthma and COPD

Supplemental material, sj-docx-1-tar-10.1177_17534666231169472 for Heterogeneity of asthma–chronic obstructive pulmonary disease (COPD) overlap from a cohort of patients with severe asthma and COPD by Joon Young Choi, Chin Kook Rhee, Kwang Ha Yoo, Ki-Suck Jung, Jae Ha Lee, Hyoung Kyu Yoon, Seung Won Ra, Myung Goo Lee and Yong Suk Jo in Therapeutic Advances in Respiratory Disease</p

Risk factors for OSA in IPF patients analyzed by the logistic regression model.

Risk factors for OSA in IPF patients analyzed by the logistic regression model.</p

Prognostic factors for mortality in patients with IPF by Cox proportional hazards model.

Prognostic factors for mortality in patients with IPF by Cox proportional hazards model.</p