Antigen avoidance and outcome of nonfibrotic and fibrotic hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is classified into nonfibrotic and fibrotic phenotypes. Patients with nonfibrotic HP often experience recurrence and develop fibrosis, whereas those with fibrotic HP have a poor prognosis. Although antigen avoidance has long been the first line of treatment for HP, its impact on prognosis has been poorly reported. METHODS: Medical records of 121 patients with HP diagnosed by new diagnostic criteria of American Thoracic Society/Japanese Respiratory Society/Asociación Latinoamericana del Tórax (ATS/JRS/ALAT) guidelines and treated at our institution in Saitama, Japan, were retrospectively analysed. HP was classified into nonfibrotic and fibrotic phenotypes and six HP subtypes: summer-type, bird-related, home-related and occupational HP, humidifier lung, and hot tub lung. Achievement of reduced exposure to inciting agents was divided into complete antigen avoidance (CAA) and incomplete antigen avoidance (IAA) by HP subtype. RESULTS: Of the 74 patients with nonfibrotic HP, 30 achieved CAA and experienced no recurrence or development of fibrosis. In the remaining 44 patients with IAA, 24 (54.5%) experienced recurrence and/or development of fibrosis. The all-cause 5-year mortality rate in the 47 patients with fibrotic HP was 47.8%. Negative prognostic factors of HP-related mortality in these patients were <50% lymphocytes in bronchoalveolar lavage (BAL) and honeycombing. Multivariate analysis showed a tendency for IAA to be related to poorer survival (hazard ratio 3.452, 95% CI 0.964-12.359, p=0.057). CONCLUSIONS: In the patients with nonfibrotic HP, CAA resulted in no recurrence or development of fibrosis and longer survival. In the patients with fibrotic HP, <50% lymphocytes in BAL and honeycombing were negative prognostic factors for mortality.

A retrospective analysis of pembrolizumab plus chemotherapy versus pembrolizumab monotherapy for advanced or recurrent non-small cell lung cancer.

BACKGROUND: Although clinical trials have investigated the addition of pembrolizumab to chemotherapy for non-small cell lung cancer, none have investigated the addition of chemotherapy to pembrolizumab. METHODS: We conducted a retrospective study of 71 NSCLC patients including 33 treated with pembrolizumab plus chemotherapy (combination therapy group) and 38 treated with pembrolizumab monotherapy (monotherapy group) from 1 May 2016 to 31 August 2020. RESULTS: Eleven of 33 (33.3%) patients in the combination therapy group and 37 of 38 (97.4%) patients in the monotherapy group had programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≥50%. Objective response rate (ORR) and median overall survival (OS) were not significantly different between the combination therapy group and monotherapy group (54.5% vs. 47.4, p = 0.637 and 16.6 vs. 27.0 months, p = 0.463). In patients with PD-L1 TPS ≥50%, ORR and median OS were not different between the combination therapy group and the monotherapy group (63.6% vs. 48.6%, p = 0.499 and not reached vs. 27.0 months, p = 0.976). Thirty-three (100%) patients experienced adverse events (AEs) in the combination therapy group and 32 (84.2%) in the monotherapy group. Treatment discontinuation at 1 year due to AEs occurred more frequently in the combination therapy group (45.2%) than in the monotherapy group (21.1%). CONCLUSION: There was no significant difference in ORR and OS between the two groups, and treatment discontinuation was more frequent in the combination group. A randomized controlled trial is needed to evaluate the addition of chemotherapy to pembrolizumab for first-line treatment in patients with PD-L1 TPS ≥50%.

Outcome and risk factor of immune-related adverse events and pneumonitis in patients with advanced or postoperative recurrent non-small cell lung cancer treated with immune checkpoint inhibitors.

BACKGROUND: Non-small cell lung cancer (NSCLC) patients with pre-existing respiratory diseases have been excluded in clinical trials of immune checkpoint inhibitor (ICI) therapy, and it is unknown whether the same degree of response can be expected as that in patients without pre-existing respiratory diseases and if they are associated with increased risk for various immune-related adverse events (irAEs) and ICI pneumonitis. This study aimed to evaluate predictive factors of clinical response, prognostic factors, risk factors of irAEs, and ICI pneumonitis in NSCLC patients with or without pre-existing respiratory diseases. METHODS: We conducted a retrospective study of 180 NSCLC patients who received ICI monotherapy of nivolumab, pembrolizumab, or atezolizumab from 1 January 2016 to 31 March 2019. RESULTS: A total of 119 patients had pre-existing respiratory diseases, including 20 with pre-existing idiopathic interstitial pneumonias (IIPs). A total of 85 patients experienced irAEs, of which ICI pneumonitis was the most frequent adverse event, occurring in 27 patients. Of the three patients who died from irAEs, all from ICI pneumonitis, two had pulmonary emphysema and one had pre-existing IIP. In multivariate analyses, irAEs were associated with objective response rate (ORR) and favorable OS, and IIPs were associated with increased risk for ICI pneumonitis. However, IIPs were not associated with low ORR or poor OS. CONCLUSIONS: Pre-existing IIPs were a risk factor for ICI pneumonitis. However, this study showed that ICI therapy can be offered to patients with pre-existing respiratory diseases with the expectation of the same degree of response as that in patients without pre-existing respiratory diseases. KEY POINTS: Significant findings of the study: Pre-existing IIPs were a risk factor for ICI pneumonitis, but objective response rate and prognosis of patients with IIPs were similar to those of other patients. WHAT THIS STUDY ADDS: In patients with pre-existing IIPs, ICI pneumonitis should be noted. However, ICI therapy can be offered to patients with pre-existing respiratory diseases with the expectation of the same degree of response as that in patients without pre-existing respiratory diseases.

Clinical course and findings of 14 patients with COVID-19 compared with 5 patients with conventional human coronavirus pneumonia.

OBJECTIVE: To clarify what future problems must be resolved and how clinical findings of SARS-CoV-2 infection differ from those of cHCoV infection. METHODS: Patients and Methods Clinical characteristics of 14 patients with laboratory-confirmed Coronavirus disease 2019 (COVID-19) and 5 patients with cHCoV pneumonia admitted to our institution and treated up to March 8, 2020, were retrospectively analyzed. RESULTS: On admission, 10 patients had pneumonia, 5 of whom had pulmonary shadows detectable only via computed tomography (CT). During hospitalization, another patient with no pulmonary shadows on admission developed pneumonia. In total, 11 (78.6%) of the 14 patients developed pneumonia, indicating its high prevalence in COVID-19. During hospitalization, the patients' symptoms spontaneously relapsed and resolved, and gastrointestinal symptoms were frequently found. C-reactive protein values showed correlation with the patients' clinical courses. Ritonavir/lopinavir were administered to 5 patients whose respiratory conditions worsened during admission, all of whom improved. However, the pneumonia in the 6 other patients improved without antivirals. None of the 14 patients died, whereas 5 other patients with cHCoV pneumonia were in respiratory failure on admission, and one patient (20%) died. CONCLUSION: Both SARS-CoV-2 and cHCoV can cause severe pneumonia. Problems for future resolution include whether antiviral agents administered in cases of mild or moderate severity can reduce the number of severe cases, and whether antivirals administered in severe cases can reduce mortality.

Development of myasthenia gravis 8 years after interstitial lung disease associated with antisynthetase (anti-EJ antibody) syndrome.

Patients with antisynthetase-positive interstitial lung disease (ILD) alone sometimes develop myositis during follow-up, but myasthenia gravis (MG) overlapping on antisynthetase syndrome is unusual. A 56-year-old woman with ILD and anti-EJ antibody treated for 8 years developed MG. Physicians should consider myositis and MG when patients develop muscle symptoms during follow-up.

Diagnostic criteria that can most accurately differentiate allergic bronchopulmonary mycosis from other eosinophilic lung diseases: A retrospective, single-center study.

BACKGROUND: Several diagnostic criteria have been proposed to differentiate allergic bronchopulmonary mycosis (ABPM) from asthma, but there have been no studies to establish diagnostic criteria to classify ABPM differently from other eosinophilic lung diseases. METHODS: We retrospectively investigated both patients with ABPM (n=42) diagnosed by clinical (Rosenberg-Patterson criteria modified to apply to fungi other than Aspergillus spp., with consideration of computed tomography and bronchoscopy findings) or pathological criteria and those with other eosinophilic lung diseases (n=118) to establish elaborate diagnostic criteria for ABPM. RESULTS: Etiologies of ABPM included fungi other than Aspergillus spp. or unidentified pathogens in 16 patients. Fourteen patients (33.3%) did not have asthma. When the diagnostic cutoff line was set to satisfy six or more primary plus secondary modified Rosenberg-Patterson criteria, ABPM could be diagnosed with good sensitivity, specificity, and positive/negative predictive values (97.6%, 98.3%, 95.3%, and 99.1%, respectively). When the diagnostic criteria were combined with pathological criteria, the values further improved to 100%, 98.3%, 95.5%, and 100%, respectively. CONCLUSIONS: Our results suggest that these novel criteria offer good sensitivity, specificity, and positive/negative predictive values for the diagnosis and classification of ABPM.

Clinical and Radiographic Comparison of Influenza Virus-associated Pneumonia among Three Viral Subtypes.

OBJECTIVE: Presently, the predominant subtypes of influenza viruses in the world, except for those in local epidemics, include influenza pandemic H1N1 2009 (pH1N1), H3N2, and B viruses. There are few reports on the differences in the clinical features, radiographic findings, treatment, and outcomes of influenza virus-associated pneumonia among these three viral subtypes. The purpose of this study was to investigate whether the clinical features, radiographic findings, treatment, and outcomes differ among the viral subtypes. METHODS: We retrospectively analyzed 96 patients with influenza virus-associated pneumonia whose viral subtypes were clarified. RESULTS: Patients with pH1N1 virus-associated pneumonia tended to be young. The frequency of primary viral pneumonia differed among the virus-associated pneumonia subtypes (pH1N1, 80%; H3N2, 26.5%; and B, 31%). Patients with pH1N1 virus-associated pneumonia more frequently showed bilateral ground-glass opacities (GGOs), which affected more lobes than in patients with H3N2 and B virus-associated pneumonia. However, patients with H3N2 virus-associated pneumonia showed a higher frequency of consolidation and diffuse bronchial wall thickening than did the patients with pH1N1 virus-associated pneumonia. The severity and mortality did not differ among the three pneumonia subtypes. CONCLUSION: In the patients who developed influenza virus-associated pneumonia, those with pH1N1 virus-associated pneumonia frequently developed primary viral pneumonia resulting in bilateral and broad areas of GGOs on imaging, whereas patients with H3N2 virus-associated pneumonia frequently showed consolidation and diffuse bronchial wall thickening on pulmonary imaging.

Etiology and Outcome of Diffuse Acute Infectious Bronchiolitis in Adults.

RATIONALE: The etiology and outcome of diffuse acute infectious bronchiolitis (DAIB) in adults is not well known. OBJECTIVES: To retrospectively review adult patients with DAIB without pneumonia, document the etiologies and outcomes, and assess the relation between DAIB and postinfectious bronchiolitis obliterans. METHODS: We retrospectively analyzed medical records of 1,664 patients with lower respiratory tract infections admitted to our institution in Saitama, Japan. DAIB was diagnosed when patients developed acute feverish lower respiratory tract infection and chest computed tomography demonstrated mainly multiple centrilobular nodules in four or more lobes. Pneumonia was diagnosed when patients developed acute feverish lower respiratory tract infection and chest computed tomography demonstrated consolidation and/or ground-glass opacities with or without centrilobular nodules. MEASUREMENTS AND MAIN RESULTS: Of the 1,664 patients, 20 (1.2%) and 1,644 (98.8%) patients were diagnosed as having DAIB and pneumonia, respectively. Of the 20 patients with DAIB, the etiology was determined in 16 (80%): 13 (65.0%) had a single pathogen and 3 (15.0%) had two pathogens. Detected organisms included Mycoplasma pneumoniae in eight (40.0%) patients, influenza virus in two (10.0%), influenza virus and Streptococcus pneumoniae in two (10.0%), Haemophilus influenzae in three (15.0%), and respiratory syncytial virus and rhinovirus in one (5.0%) patient. All patients improved and none developed postinfectious bronchiolitis obliterans. CONCLUSIONS: The three most common etiologies of DAIB in the studied adults were M. pneumoniae, influenza virus, and H. influenzae. None of the patients with DAIB developed postinfectious bronchiolitis obliterans.

Development of multi-organ involvement including a left atrial myxoma-like lesion in a patient with granulomatosis with polyangiitis.

A 76-year-old woman suffering from granulomatosis with polyangitis (GPA) developed organizing pneumonia with positive antineutrophil cytoplasmic antibodies and microscopic hematuria. Prednisolone improved the hematuria and radiological findings; however, after tapering the dose of prednisolone, a posterior left atrial wall mass was detected in association with a fever. Both regressed spontaneously, although secretory otitis media and sinusitis were noted; the resected sinusitis specimen exhibited vasculitis highly suggestive of GPA. The clinical picture of GPA with multi-organ involvement can vary. Recognizing the various manifestations of GPA is therefore necessary in order to provide an appropriate diagnosis and disease management.

ß2-adrenergic receptor haplotype may be associated with susceptibility to desensitization to long-acting ß2-agonists in COPD patients.

PURPOSE: Τhat ß2-adrenergic receptor (ß2AR) haplotypes may play a key role in clinical response to ß2-agonists and haplotype Cys-19Gly16Gln27 (CysGlyGln) is reported to be associated with desensitization of ß2AR to ß-agonists in lymphocytes isolated from patients with asthma and septic shock. We sought to determine whether haplotypic variation of the ß2AR affects the functional outcomes of long-acting ß2-agonist (LABA) treatment for chronic obstructive pulmonary disease (COPD) when used as monotherapy. METHODS: Treatment-naïve patients with COPD (n = 36) were prospectively treated with two kinds of LABA--inhaled salmeterol and transdermal tulobuterol patch--for 12 weeks in crossover study, and changes in pulmonary function data and 6-minute walk distance (6 MWD) were compared between groups stratified by the CysGlyGln. RESULTS: Frequencies of haplotype and diplotype for the CysGlyGln were 0.51 and 0.36, respectively. The individuals homozygous for CysGlyGln showed less improvement in FEV(1), %FEF(25-75 %), and IC/TLC than those with 0 or 1 copy of CysGlyGln after treatment with both LABAs despite initial bronchodilator responses to albuterol being similar in these groups. The response in these parameters was not significantly different between two types of LABA. Overall changes in 6 MWD in individuals with 2 copies of CysGlyGln versus 0 or 1 copy for salmeterol were 2.8 and 11 m, and for tulobuterol were -1.3 and 16 m, respectively. CONCLUSIONS: Homozygous haplotype for the CysGlyGln of ß2AR may be associated with susceptibility to desensitization to LABA in patients with COPD.

Two cases with solitary pulmonary nodule due to non-tuberculous mycobacterial infection showing intense 18F-fluorodeoxyglucose uptake on positron emission tomography scan.

We report an 81-year-old man and a 65-year-old woman with a solitary pulmonary nodule (SPN) due to infection with non-tuberculous mycobacteria (NTM). In each case, the nodule showed a high (18)F-fluorodeoxyglucose (FDG) uptake with the maximum standardized uptake values (SUV) of 13.2 and 4.8 on positron emission tomography (PET) imaging, respectively. Both cases required partial lung resection for confirmation of the histological diagnosis. A review of six reported patients with SPN due to NTM infections showed that the SUV of FDG was more than 4.0 in the nodules of all cases. Positive results on FDG-PET should be interpreted cautiously when evaluating SPN, especially in patients having predisposing factors for NTM infections.

A retrospective analysis of clinical outcomes of patients older than or equal to 80 years with small cell lung cancer.

INTRODUCTION: The optimal treatment for patients older than 80 years with small cell lung cancer (SCLC) is unknown. METHODS: A retrospective chart review was conducted for 45 patients aged 80 years or older with SCLC, and therapeutic indices and toxicities of anticancer treatment were compared with those of 38 patients aged 70 to 79 years. Subgroup analyses according to the levels of performance status (PS) and comorbidity were also performed. RESULTS: Twenty-four (53%) of the 45 patients underwent combination chemotherapy and/or thoracic radiotherapy, which resulted in significant survival benefit compared with those left untreated (p < 0.01). The main reasons for not administrating anticancer treatments were advanced age (>85 years), poor PS, and severe comorbidities. The average total chemotherapy dose delivered was 60% of the intended protocol dose. Median survival time and 1-year survival of the treated patients were 13.0 months and 57% for limited disease and 10.3 months and 40% for extensive disease, respectively. Despite a lower chemotherapy dose being administered, survival indices were similar to those of patients aged 70 to 79 years. Survival benefit was observed even in the treated patients with PS 2 to 3 or a moderate degree of comorbidity compared with those left untreated. The frequency of grade 3 to 4 hematologic toxicities was not significantly different between the two age groups. CONCLUSIONS: The standard chemotherapy regimen with or without thoracic radiotherapy seems to be feasible for patients older than 80 years with SCLC, even for those with PS 2 to 3 and/or moderate comorbidity, although frequent dose adjustment is necessary.

Lower incidence of acute respiratory distress syndrome in community-acquired pneumonia patients aged 85 years or older.

UNLABELLED: Clinical variables and laboratory data were compared to elucidate the risk factors associated with the development of ARDS among elderly patients with community-acquired pneumonia (CAP). The predictors for ARDS appeared to differ from the determinants of severity of CAP. ARDS developed less frequently among patients aged>or=85 years. BACKGROUND AND OBJECTIVE: The incidence of and risk factors for ARDS among elderly patients with community-acquired pneumonia (CAP) have not been well characterized. METHODS: The clinical details of 221 consecutive patients aged>or=65 years, who were admitted with CAP during the period April 2006 to June 2008, were investigated by review of patient charts. Clinical variables and laboratory data at admission for CAP were compared between patients with and without ARDS. RESULTS: Eighteen patients (8.1%) developed ARDS 1-5 days after admission. The mortality rate was 44% in patients with ARDS and 10.3% in those without ARDS (P<0.001). The incidence of ARDS was 8.5-20% among patients aged<85 years and 1.1% in patients aged>or=85 years (P<0.001), while overall mortality rates were not significantly different among the age groups. Predictors for the development of ARDS included higher serum levels of CRP and glucose, lower PaO2/fraction of inspired O2 (FiO2), PaCO2 and HCO3-, and the presence of systemic inflammatory response syndrome at admission. ARDS developed less frequently among patients with pneumonia associated with oropharyngeal aspiration (AP). Multivariate analysis indicated that lower age, serum glucose, pre-existence of systemic inflammatory response syndrome and non-oropharyngeal AP were significant risk factors for ARDS. The Pneumonia Severity Index and confusion, urea, respiratory rate, blood pressure, age>or=65 score were not correlated with the incidence of ARDS. CONCLUSIONS: Predictors for ARDS appeared to differ from the determinants of severity of CAP in the elderly. ARDS developed less frequently in patients aged>or=85 years and in those with oropharyngeal AP. It is important to identify subjects at high risk for ARDS upon admission and to observe them closely.

Severe hyponatremia due to inappropriate secretion of antidiuretic hormone following pleurodesis.

A 69-year-old man was diagnosed as having syndrome of inappropriate secretion of antidiuretic hormone (SIADH) (serum sodium: 113 mEq/L) 13 days after a right upper lobectomy due to squamous cell carcinoma of the lung (pT1N0M0, stage IA) whereas the preoperative serum sodium level was nearly normal. He had undergone pleurodesis by instillation of OK432 at 2 and 5 days after surgery for prolonged air leakage. Since other possible causes of SIADH, such as residue of lung cancer, pulmonary infections, brain disorders, or known causative drugs were ruled out, the SIADH in this patient was likely associated with pleurodesis by the use of OK-432. A review of similar cases reported suggests that it is important to be aware of the possibility of severe hyponatremia due to SIADH after chemical pleurodesis.