Clinical Manifestations and Prognostic Factors of Pneumocystis jirovecii Pneumonia without HIV.

INTRODUCTION: Pneumocystis jirovecii pneumonia (PCP) can occur in HIV patients but also in those without HIV (non-HIV PCP) but with other causes of immunodeficiency including malignancy or rheumatic diseases. OBJECTIVE AND METHODS: To evaluate the clinical presentation and prognostic factors of non-HIV PCP, we retrospectively reviewed all patients diagnosed as having PCP without HIV at Kameda Medical Center, Chiba, Japan, from January 2005 until June 2012. For the purpose of examining a prognostic factor for non-HIV PCP with 30-day mortality, we compared the characteristics of patients, clinical symptoms, radiological images, Eastern Cooperative Oncology Group performance status (PS), and the time from the onset of respiratory symptoms to the start of therapy, in both survival and fatality groups. RESULTS: A total of 38 patients were eligible in this study. Twenty-five survived and 13 had died. The non-HIV PCP patients in the survivor group had a better PS and received anti-PCP therapy earlier than those in the nonsurvivor group. Rales upon auscultation and respiratory failure at initial visits were seen more frequently in the nonsurvivor group than in the survivor group. Lactate dehydrogenase and C-reactive protein values tended to be higher in the nonsurvivor group, but this was not statistically significant. Multivariate analyses using 5 variables showed that a poor PS of 2-4 was an independent risk factor for non-HIV PCP patients and resulted in death (odds ratio 15.24; 95% confidence interval 1.72-135.21). CONCLUSION: We suggest that poor PS is an independent risk factor in non-HIV PCP, and a patient's PS and disease activity may correlate with outcome.

Loop-mediated isothermal amplification method for diagnosing Pneumocystis pneumonia in HIV-uninfected immunocompromised patients with pulmonary infiltrates.

Loop-mediated isothermal amplification (LAMP) is becoming an established nucleic acid amplification method offering rapid, accurate, and cost-effective diagnosis of infectious diseases. We retrospectively evaluated 78 consecutive HIV-uninfected patients who underwent LAMP method for diagnosing Pneumocystis pneumonia (PCP). Diagnosis of PCP was made by the detection of Pneumocystis jirovecii (P. jirovecii) with positive LAMP or conventional staining (CS) (Grocott methenamine silver staining or Diff-Quick™) on the basis of compatible clinical symptoms and radiologic findings. Additionally, we reviewed HIV-uninfected immunocompromised patients who underwent subcontract PCR as a historical control. LAMP was positive in 10 (90.9%) of 11 positive-CS patients. Among 13 negative-CS patients with positive LAMP, 11 (84.6%) had PCP, and the remaining 2 were categorized as having P. jirovecii colonization. LDH levels in negative-CS PCP were higher than in positive-CS PCP (p = 0.026). (1 → 3)-ß-D-glucan levels in negative-CS PCP were lower than in positive-CS PCP (p = 0.011). The interval from symptom onset to diagnosis as PCP in LAMP group (3.45 ± 1.77 days; n = 22) was shorter than in subcontract PCR group (6.90 ± 2.28 days; n = 10; p < 0.001). As for patients without PCP, duration of unnecessary PCP treatment in LAMP group (2; 2-3 days; n = 10) was shorter than in subcontract PCR group (7; 7-12.25 days; n = 6; p = 0.003). LAMP showed higher sensitivity (95.4%) and positive predictive value (91.3%) than subcontract PCR did. Pneumocystis LAMP method is a sensitive and cost-effective diagnostic method and is easy to administer in general hospitals. In-house LAMP method would realize early diagnosis of PCP, resulting in improving PCP prognosis and reducing unnecessary PCP-specific treatment.

Modified MRC assessment and FEV1.0 can predict frequent acute exacerbation of COPD: An observational prospective cohort study at a single-center in Japan.

INTRODUCTION: Acute exacerbation (AE) of chronic obstructive pulmonary disease (COPD) is a fatal event, leading to poor outcomes among COPD patients. However, exact frequency and poor prognostic factors are not well known in Japan. METHODS: and patients, To assess the frequency and risk factors of AE, we performed this prospective cohort study at the Kameda Medical Center in Japan between during 2011 and 2013. AE was defined as an acute worsening of respiratory symptoms according to the GOLD guideline. Furthermore, we compared the exacerbation-free time between the groups. RESULTS: A total of 330 patients (230 COPD patients and 100 smoking controls) were enrolled in the study. The mean age in the study was 73 years, and 94% of the patients were male. As for the frequency of AE, 0.17 times/patients/year was found in all patients. The frequency of AE increased as the COPD disease severity (p = 0.042 by Jonch-Heere terpla test). GOLD I patients had longer exacerbation-free time than GOLD II, and GOLD II grade COPD patients had longer exacerbation-free time than GOLD III grade COPD patients. In terms of risk factors for AE, logistic regression analysis showed that Modified Medical Research Council (mMRC) scale ≥3 and FEV1.0% <50% were independent poor prognostic factors for moderate grade of AE events, and mMRC scale ≥3 was independent poor prognostic factor for severe AE events. CONCLUSION: The frequency of AE increases as the disease severity becomes more severe. We found mMRC scale >3 and FEV1 <50% were risk factors for AE-COPD.

A case of novel swine influenza A (H1N1) pneumonia complicated with virus-associated hemophagocytic syndrome.

Influenza related to complications such as pneumonia and encephalitis have sporadically been reported. However, influenza A (H1N1)-virus-associated hemophagocytic syndrome (VAHS) has rarely been reported. A 39-year old woman complained of high fever and was referred to us. Chest infiltrations in both lungs and a positive polymerase chain reaction (PCR) for novel swine origin influenza A (H1N1) in bronchial alveolar lavage fluid (BALF) specimen was confirmed and she was diagnosed with influenza A (H1N1) pneumonia. Pancytopenia was found, and hemophagocytic syndrome (HPS) was diagnosed by bone marrow aspiration. Following intravenous administration of antiflu drug and combination therapy of steroid pulse and erythromycin IV, the patient's respiratory dysfunction and lab data gradually improved and she was discharged on day 21. Whereas secondary HPS related to viral infections such as Epstein­Barr virus, cytomegalovirus, and human herpesvirus type 6 are commonly seen, H1N1 pneumonia complicated with secondary VAHS is rare.

Early diagnosis and treatment are crucial for the survival of Pneumocystis pneumonia patients without human immunodeficiency virus infection.

The mortality of Pneumocystis pneumonia (PCP) patients without human immunodeficiency virus (HIV) infection ranges from 0 to 70 %, whereas that of HIV-infected PCP patients ranges from 10 to 20 %. The reasons for these differences are not known. We retrospectively analyzed factors contributing to the survival of 23 patients with PCP and without HIV infection, in whom PCP developed as community-acquired pneumonia (CAP). The interval from admission to the start of PCP-specific treatment was significantly shorter for survivors (2.71 ± 3.64 days; n = 14) than for non-survivors (8.67 ± 5.5 days; n = 9; p = 0.003). Moreover, although the severity scores/classes assessed by A-DROP, CURB-65, and PSI were no different on admission, scores/classes at the start of PCP-specific treatment were significantly higher for non-survivors. Overall mortality was 39 %, but mortality was approximately 70-100 % for patients classified as severe grade by A-DROP, CURB-65, or PSI scores/classes at the time when PCP-specific treatment was started, which was far higher than expected for these guidelines. In conclusion, early diagnosis and treatment within 3 days are crucial for the survival of PCP patients without HIV infection. We emphasize the limitations of application of guidelines for CAP to patients with PCP.

A successful diagnostic case of Pneumocystis pneumonia by the loop-mediated isothermal amplification method in a patient with dermatomyositis.

Pneumocystis pneumonia (PCP) can occur in patients with many causes of the immunocompromised state other than human immunodeficiency virus (HIV). It is quite difficult to diagnose PCP without HIV because there is no method for detecting Pneumocystis jirovecii. Thus, non-HIV PCP continues to have high mortality. Recently, loop-mediated isothermal amplification (LAMP) is becoming an established nucleic acid amplification method offering rapid, accurate, and cost-effective diagnosis of infectious diseases. We report a non-HIV PCP case successfully diagnosed by the LAMP method. It was previously reported that PCR in BALF specimens had been the most sensitive method in the diagnosis of PCP without HIV. The LAMP method would be more sensitive than conventional PCR and an effective tool in the early diagnosis of PCP.

Pathophysiological mechanism of non-HIV Pneumocystis jirovecii pneumonia.

While Pneumocystis jirovecii pneumonia (PCP) can occur in immunocompromised patients with HIV infection, the prognosis of non-HIV PCP is still poor, showing a high mortality rate of 30%-75%. The pathophysiological mechanism of non-HIV PCP is quite different from that of HIV-PCP. Aging, underlying disease, dysbiotic gut microbiome, and Th1 predominance, leads to macrophagic polarization shifting from M2 to M1. These cause dysregulation in the host immunity against P. jirovecii, resulting in severe lung injury and a high mortality rate among non-HIV PCP patients. This review describes poor prognostic factors, an issue of predictive values used for general pneumonia practice, and new aspects, including the dysbiosis of the gut microbiome and macrophagic polarization in the treatment of non-HIV PCP.

Efficacy and safety of single-dose 2.0 g azithromycin in the treatment of acute exacerbation of chronic obstructive pulmonary disease.

To evaluate the efficacy and safety of single-dose 2.0 g azithromycin (ZSR) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), we retrospectively reviewed all patients with AE-COPD who were treated with ZSR. In comparison with patients who received intravenous therapy for AE-COPD, the clinical cure rate, length of stay in hospital, and medical costs were evaluated. A total of 29 patients thus were eligible for this study. Clinical cure rates of ZSR and intravenous therapy for the treatment of AE-COPD were 83.3% (n = 12) and 88.2% (n = 17), respectively, between the groups (P = 1.000). No severe adverse events were found in either group. The ZSR and intravenous groups averaged 9.9 and 12.5 days of admission, respectively. Length of admission for clinical success cases was much shorter for patients who received ZSR than patients who received intravenous therapy (6.2 vs. 11.9 days, P = 0.038). Medical costs were less for the group receiving ZSR than for the intravenous therapy group. We suggest ZSR can achieve near-perfect compliance and could be one of the tools in the treatment of AE-COPD.

A case of asthma-complicated influenza myocarditis.

A 36-year-old man with a history of asthma visited an outpatient clinic complaining of high fever and general fatigue, and was diagnosed as having influenza type A by influenza antigen test. Laboratory findings revealed mild inflammation, mild acidemia, and hypercapnea with radiologic infiltrations in the right lung, and remarkable wheezes in both lungs were heard on auscultation. He was diagnosed with asthma exacerbation and having influenza pneumonia, and was referred to us. Therapy was begun with oseltamivir for influenza infection and intravenous infusions of betamethasone and aminophylline with non-invasive pulmonary ventilation for asthma exacerbation and acute respiratory failure. Although he was weaned from mechanical ventilation and his general condition became good, electrocardiogram showed sinus bradycardia and negative T waves in V1-4 without any symptoms. Blood test and echocardiography showed almost normal findings except for slight elevation of LDH and AST. Influenza A antigen was already confirmed and he was diagnosed as having influenza myocarditis clinically. Although it is well known that influenza can cause asthma exacerbation and encephalopathy, influenza myocarditis is regarded as rare by physicians. In fact, the number of case reports about influenza myocarditis is few. Myocarditis may not appear to be serious, but could cause fatal arrhythmia and heart failure. All clinicians should be aware of the overall clinical picture and the possibility of severe complications of myocarditis caused by flu infection.

[Relationship between the prognosis of interstitial pneumonia and its comorbidities].

BACKGROUND: To investigate the relationship between the prognosis of chronic interstitial pneumonia (IP) and its comorbidities, we conducted a retrospective study for clinically and radiologically diagnosed IP. We assessed comorbidities by using the Charlson Comorbidity Index (CCI). METHODS: We classified 224 patients given clinical diagnoses of chronic IP (excluding the patients who had clear causes such as collagen disease, infection, drugs or radiation) in our institution between April 2000 and June 2010, into 2 groups; those with clinical diagnoses of idiopathic pulmonary fibrosis (IPF:108 cases) and those with other chronic IP but without honeycomb lung (116 cases); and analyzed their backgrounds and comorbidities. We also classified them into survival and non-survival groups to assess their prognostic factors. RESULTS: Although the smoking status of patients with clinically diagnosed IPF was higher, and SpO2 was lower than those with other chronic IP without honeycomb lung, the mean age, comorbidities and CCI did not differ between them. The 5-year overall survival of the clinically-diagnosed IPF group was lower than that of the other chronic IP without honeycomb lung group (50.8% vs. 76.3%, p<0.01). In cases of other chronic IP without honeycomb lung, the CCI of non-survival cases was higher than that of survival cases (4.05 vs. 2.47, p<0.01), although patient backgrounds did not differ between survival and non-survival cases in those with clinically diagnosed IPF (CCI : 2.32 vs. 2.98, p = 0.70). CONCLUSIONS: Our analysis revealed the possibility that comorbidities and CCI were prognostic factors in other chronic IP cases without honeycomb lung, although the prognosis of IPF was not affected by their comorbidity.

[Two cases of type I respiratory failure managed by the highFO nebulizer].

Among conventional oxygen therapies there are currently no devices which can supply a high oxygen level of over 60%. The HighFO nebulizer (Koike Medical) is a new device which is able to supply an oxygen flow rate of over 35l/min, and a high concentration of oxygen. We report 2 cases of type I respiratory failure managed by the HighFO nebulizer. Case 1: A 70-year-old man with lung cancer had an acute exacerbation of radiation pneumonitis during chemoradiotherapy. We gave him an oxygen mask with a reserve bag, but his condition worsened. We then used the HighFO nebulizer followed by non-invasive positive pressure ventilation. He began to recover and we again used the HighFO nebulizer during the weaning period. Case 2: A 74-year-old man presented with acute exacerbation of interstitial pneumonitis. We started steroid pulse therapy, HighFO nebulizer treatment and physiotherapy to prevent disuse syndrome. We were able to raise his exercise stress levels due to the high concentration of oxygen provided by the HighFO nebulizer. We believe that the HighFO nebulizer is useful for type-I respiratory failure as well as interstitial pneumonia. However, oxygen toxicity is a potential problem, so we must accumulate more cases in order to fully assess the risks and benefits of this new modality.

[The efficacy of shortening an administration period with omalizumab].

A 64-year old male who had been treated with oral predisolone for severe bronchial asthma had started the treatment of omalizumab administration every 4 weeks since December 2009 and his symptoms had prominently improved. However, he complained the recurrence of his symptoms 4 weeks after administration of omalizumab and the mean times of SABA use had also increased from 0.61/day (1-2w) to 0.95/day (4w). Therefore, we had shortened the interval of omalizumab to 3 from 4 weeks since April 2010. Consequently, his symptoms have improved with increase of Asthma Control Test (15.67→21.33) and it has been possible to reduce the oral prednisolone. Recently, we can use the omalizumab and have extended the choice of treatment for severe bronchial asthma. However, it is predicted that there are some patients who have clinical problems for continuing the recommendation dose or intervals. We report a case with a brief review of the literature.

[A clinical review of pleurodesis for patients with poor performance status].

BACKGROUND: Although pleurodesis is an effective treatment for malignant pleural effusion, we hesitate to use in patients with poor performance status (PS) because of its side effects. METHODS: Of 46 pleurodesis cases in our institution between 2006 and 2010, 24 poor PS cases (>3) were classified into 2 groups according to survival (beyond 3 months) or non-survival, and 3 groups according to condition: PS improved after pleurodesis, remained stable, or was exacerbated and we analyzed their backgrounds. RESULTS: Among the 24 cases (66.7%), there were 5 and 19 survival and non-survival cases. Patient backgrounds, characteristics of the lesions and examination results did not differ significantly among them. On the other hand, the ratio of successful initial pleurodesis in the exacerbated PS group was lower than in the improved and stable groups (16.7% vs. 100%, 87.5%). The 1- and 3-month survival rates of unsuccessful cases were lower than those of successful cases (33.3% vs. 77.8%, 0% vs. 32.4%). CONCLUSION: Success of initial pleurodesis can affect PS and outcome, thus it is important to improve the number of successful cases of initial pleurodesis.

[Splenic metastasis of lung cancer].

A 71-year-old man was referred for a chest x-ray of the right upper lobe lung mass in August 2005. Bronchoscopy and transbronchial biopsy revealed squamous cell carcinoma. A routine metastatic workup revealed his clinical stage to be IIIA (cT2N2M0). We treated him with chemotherapy and radiotherapy. However, an abdominal CT scan showed an 8 cm nodule in the spleen in June 2006. Splenic metastasis from lung cancer is rare. Only 13 cases have been reported from 1990 to 2008. Four of 6 cases (67%) who did not have splenectomy reported splenic rupture and had poor outcomes. Therefore, we considered that splenectomy could possibly improve the prognosis of this patient with isolated splenic metastasis. We report a case with a brief review of the literature and summarize the 13 reported cases.

[Cryptococcemia with a severe bronchial asthma: case report and review of the literature].

A 64-year old hospitalized male for severe bronchial asthma began to complain fatigue and appetite loss. His asthma had been treated with oral bethamethasone. The Chest CT at this time revealed a bilateral consolidation of the lower lung. Despite a week of treatment with antibiotics and anti-fungals, the patient expired from DIC progression. His premortem sputum and blood culture grew Cryptococcus Neoformans. We concluded his diagnosis as cryptococcal pneumonia and sepsis. Sepsis by Cryptococcus neoformans is a rare clinical event, and only 20 cases have been reported in Japan. Although 16 of the 20 had preexisting medical conditions, a case with underlying bronchial asthma has never been reported. A comparison of the reported cases of the US and Europe to that of Japan revealed differences in the patients' underlying conditions. We report a case with a brief review of the literature and summarize the 20 cases that have been reported in Japan.

[The efficacy of influenza vaccine for acute exacerbation of chronic obstructive lung disease in elderly patients].

OBJECTIVE: Acute exacerbations adversely affect the quality of life and prognosis of patients with chronic obstructive lung disease (COPD). Prevention of future exacerbations is extremely important, especially for elderly patients. In this study, we evaluated the efficacy of influenza vaccine for acute exacerbation of COPD in elderly patients. METHODS: A prospective cohort study was conducted among 289 patients over 65 years of age with COPD (FEV1/FCV<0.70) during the 2001-2002 influenza season. Background data, outpatient visits for wheezing and hospitalizations were compared between the vaccinated group (n = 189) and the unvaccinated group (n = 100). RESULTS: The number of patients who visited hospital for wheezing was 11 of 189 (5.8%) in the vaccinated group and 23 of 100 (23%) in the unvaccinated group (RRR: relative risk reduction 74.7%, 95% CI: confidence interval 0.51-0.87). The number of hospitalizations for pneumonia was 8 of 189 (4.2%) in the vaccinated group and 14 of 100 (14%) in the unvaccinated group (RRR 69.8%, 95% CI: 0.32-0.87). The costs of hospitalization were lower in the vaccinated group with direct savings of 91,525 yen per patient. CONCLUSIONS: For elderly COPD patients, influenza vaccine decreases acute exacerbation due to pneumonia and bronchoconstriction, and also may minimize the costs of hospitalization.

Familial Summer-type Hypersensitivity Pneumonitis: A Review of 25 Families and 50 Cases in Japan.

Summer-type hypersensitivity pneumonitis (SHP) is the most common form of pneumonitis in Japan; it accounts for 74% of all cases. It has been reported that 19.5-23.8% of SHP cases occur in families who live in the same house. We present our SHP cases and review 50 familial cases in 23 families that were reported in Japan (including our own) and 48 cases that were previously described in 22 articles published between January 1982 and October 2011. To the best of the authors' knowledge, this is the first review article in English to document the familial occurrence of SHP in Japan.

Rice-Field Drowning-Associated Pneumonia in which Pseudomonas spp., Aspergillus fumigatus, and Cunninghamella sp. Are Isolated.

We herein report the case of an 84-year-old who developed pneumonia after drowning in a rice field. Besides Aspergillus fumigatus, many pathogens previously not reported in drowning-associated pneumonia (such as Pseudomonas fluorescens, Pseudomonas putida, Nocardia niigatensis, and Cunninghamella sp.) were isolated from his sputum. He received sulbactam/ampicillin, trimethoprim/sulfamethoxazole, voriconazole, levofloxacin and liposomal amphotericin B, but died due to respiratory failure. Because the patient had drowned in a contaminated stagnant rice field and had multiple lung cavities, zygomycosis was suspected. This report provides invaluable information for the consideration of zygomycosis after an individual drowning in a rice field, even in an immunocompetent patient.

Successful treatment of non-small cell lung cancer with gefitinib after erlotinib-induced severe eyelid erosion: Two case reports.

Gefitinib and erlotinib are first-generation, small, molecular inhibitors of the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Even as these drugs have led to a paradigm shift in the treatment of advanced non-small cell lung cancer (NSCLC), drug-induced adverse effects are commonly seen. We experienced two cases of NSCLC patients who developed erlotinib-induced eyelid erosion and were then successfully treated with gefitinib, without recurrence of toxicity or disease progression. As far as we had investigated, this is the first report documenting the successful cases treated with gefitinib after erlotinib-related severe eyelid erosion.

Implementation of do not attempt resuscitate orders in a Japanese nursing home.

OBJECTIVE: To investigate whether do not attempt resuscitation (DNAR) orders can be implemented in a standard nursing home in Japan, where routine DNAR orders are not yet common in many facilities including hospitals. METHOD: Ninety-eight residents in a 100-bed nursing home were evaluated. All of the eligible residents and/or their family members were asked whether they wanted to receive resuscitation, including mechanical ventilation. RESULT: The residents were 54 to 101 years of age (mean 83.3), with 27 males and 71 females. After administering the questionnaire, 92 (94%) patients did not want resuscitation and mechanical ventilation. CONCLUSION: In a nursing home, it was possible to obtain advance directives by which most residents/families rejected resuscitation and mechanical ventilation. This could avoid unnecessary and undesirable resuscitation procedures.