Intravenous immunoglobulin for acute exacerbation of fibrotic idiopathic interstitial pneumonias.

BACKGROUND AND AIM: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a fatal condition with no established treatment. Intravenous immunoglobulin (IVIG) is a unique therapy with both anti-inflammatory and anti-infective effects. Therefore, we hypothesized that IVIG may have a positive effect on AE of interstitial pneumonia. This study aimed to determine the effect of IVIG in patients with AE of fibrotic idiopathic interstitial pneumonias (IIPs), including IPF. METHODS: We retrospectively analyzed consecutive patients who were diagnosed with AE of fibrotic IIPs and treated with pulse corticosteroid therapy (methylprednisolone 500-1000 mg/day for 3 days) between April 2018 and May 2021 at Kagawa Rosai Hospital and KKR Takamatsu Hospital. RESULTS: This study included 52 patients with AE of fibrotic IIPs (IPF,41; fibrotic IIPs other than IPF,11). Thirteen patients received IVIG (5 g/day for 3-5 days) concurrently with pulse corticosteroid therapy. The remaining 39 patients were assigned to the control group. The survival rate on day 90 was significantly higher in the IVIG group than that in the control group (76.9% vs. 38.5%, p = 0.02). IVIG administration (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.02-0.69; p = 0.02) and C- reactive protein (OR, 1.19; 95% CI, 1.06-1.33, p < 0.01) were independently associated with 90-day mortality. CONCLUSIONS: The results indicate that administration of IVIG may improve the survival of patients with AE of fibrotic IIPs. We are now conducting a prospective study to confirm the effect of IVIG on AE of IPF since May 2022 (jRCT1061220010).

Outcomes and predictive factors for successful smoking cessation therapy in COPD patients with nicotine dependence.

BACKGROUND: The data on smoking cessation treatment outcomes for smokers with chronic obstructive pulmonary disease (COPD) are limited. The present study assessed the effectiveness of smoking cessation interventions at our clinic. METHODS: Data from a prospective registry of a 3-month smoking cessation program were evaluated. The primary outcome, smoking cessation, was defined as the complete abstinence from smoking between the 8-week and 12-week clinic visits. Pulmonary function and health-related quality of life using St. George's Respiratory Questionnaire (SGRQ) were assessed at baseline and at the end of the program. RESULTS: Out of the 155 COPD patients with nicotine dependence (female/male = 39/116; mean age, 67.2 ± 9.8 years; mean forced expiratory volume in 1 s (FEV1), 59.7 ± 21.1% predicted), 107 participants completed the program. Among the completers, 74 achieved smoking cessation. In the multivariate analysis, mental disorders (odds ratio [OR] 3.678, 95% confidence interval [CI]: 1.182, 11.445), higher exhaled carbon monoxide (CO) level (OR 1.080, 95% CI: 1.013, 1.151) and lower FEV1/forced vital capacity (FVC) (OR 0.958, 95% CI: 0.923, 0.995) were negatively associated with successful smoking termination. Significant changes in pulmonary function were found in quitters but not in continuous smokers (increases in FEV1 by 0.09 L/s [95% CI: 0.03, 0.15] and peak expiratory flow by 0.23 L/s [95% CI: 0.01, 0.44]). SGRQ total scores improved significantly in both quitters (-5.4 [95% CI: -8.4, -2.5]) and continuous smokers (-7.0 [95% CI: -11.6, -2.5]). CONCLUSION: In the program completers, the exhaled CO levels, FEV1/FVC ratio, and presence of mental disorders were significantly associated with program success or failure in COPD patients with nicotine dependence.

Impact of urinary tract infection on nursing and healthcare-associated pneumonia.

Nursing and healthcare-associated pneumonia (NHCAP), a concept of pneumonia proposed by the Japanese Respiratory Society, mostly occurs among elderly people in long-term care facilities. Similarly, the risk of urinary tract infection (UTI) also increases with age, with UTIs common among those in long-term care. Therefore, NHCAP is sometimes complicated by the presence of a UTI. However, pneumonia complicated by a UTI has not been clinically well characterized. We retrospectively analyzed 376 patients with NHCAP admitted to our hospital over a three-year period. Sixty-seven patients (17.8%) showed complications by a UTI. Patients with a UTI had lower renal function (higher blood urea nitrogen [P = 0.001], higher creatinine [P = 0.001]), lower systolic blood pressure (P = 0.04), higher A-DROP scores (P = 0.005) and higher positive blood culture rates (P = 0.03) than those without a UTI. Furthermore, based on urine, sputum and blood culture results, nearly half of the microorganisms (4/7) in blood cultures were identical with those of urine, suggesting that a concurrent UTI increases positive blood culture rates. Multivariate analysis showed that UTI was not an independent factor associated with 30-day mortality (P = 0.17), although patients with a UTI showed higher 30-day mortality (P = 0.04) than those without a UTI in univariate analysis. In summary, patients with NHCAP and a UTI were more prone to complications than those without a UTI, although UTI itself did not affect the prognosis of patients with NHCAP. A concurrent UTI had a negative impact on the severity of NHCAP.

Ten-year experience of smoking cessation in a single center in Japan.

BACKGROUND: Long-term, real-world data, as opposed to academic or research data, on outcomes of smoking cessation clinics are scarce. We assessed patient outcomes over a 10-year period at a smoking cessation clinic in a community teaching hospital in Japan and explored predictors of successful smoking cessation. METHODS: We used data from a prospective registry of cigarette smokers who participated in a 3-month smoking cessation program comprising combined pharmacological treatment and cognitive behavioral therapy and explored factors associated with program execution and successful smoking cessation. The primary outcome was smoking cessation, defined by quitting completely between the 8-week and 12-week sessions, with verification according to exhaled carbon monoxide (CO) level of ≤10 ppm. RESULTS: Between August 2007 and December 2017, 813 patients with nicotine dependence participated in the program. The number of participants decreased after Japan׳s 2010 tobacco tax increase. Among participants, 433 (53.3%) completed the program. In multivariate analysis, the number of cigarettes smoked daily (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.96, 0.99), cardiovascular disease (OR 1.75, 95% CI 1.16, 2.68), chronic obstructive pulmonary disease (OR 1.74, 95% CI 1.10, 2.78), and gastric/duodenal ulcer (OR 1.77, 95% CI 1.04, 3.08) were significantly associated with program completion. Among program completers, 288 (66.5%) achieved smoking cessation. Exhaled CO level (OR 0.94, 95% CI 0.93, 0.97) and mental disorders (OR 0.53, 95% CI 0.33, 0.85) were negatively associated with successful smoking cessation. CONCLUSIONS: Baseline exhaled CO level and mental disorders were significantly associated with either success or failure of smoking cessation.

Copper-catalyzed electrophilic amination using N-methoxyamines.

Copper-catalyzed electrophilic amination of a triarylboroxin using an N-methoxyamine to give quick access to a variety of anilines was reported. The reaction was especially useful for syntheses of functionalized anilines when combined with our previously reported nucleophilic addition to N-methoxyamides.

Chemoselective reductive nucleophilic addition to tertiary amides, secondary amides, and N-methoxyamides.

As the complexity of targeted molecules increases in modern organic synthesis, chemoselectivity is recognized as an important factor in the development of new methodologies. Chemoselective nucleophilic addition to amide carbonyl centers is a challenge because classical methods require harsh reaction conditions to overcome the poor electrophilicity of the amide carbonyl group. We have successfully developed a reductive nucleophilic addition of mild nucleophiles to tertiary amides, secondary amides, and N-methoxyamides that uses the Schwartz reagent [Cp2 ZrHCl]. The reaction took place in a highly chemoselective fashion in the presence of a variety of sensitive functional groups, such as methyl esters, which conventionally require protection prior to nucleophilic addition. The reaction will be applicable to the concise synthesis of complex natural alkaloids from readily available amide groups.

Total synthesis of (±)-gephyrotoxin by amide-selective reductive nucleophilic addition.

A chemoselective approach for the total synthesis of (±)-gephyrotoxin has been developed. The key to success was the utilization of N-methoxyamides, which enabled the direct coupling of the amide with an aldehyde and selective reductive nucleophilic addition to the amide in the presence of a variety of sensitive and electrophilic functional groups, such as a methyl ester. This chemoselective approach minimized the use of protecting-group manipulations and redox reactions, which resulted in the most concise and efficient total synthesis of (±)-gephyrotoxin described to date.