Characteristics and risk factors for Pneumocystis jirovecii pneumonia in patients with idiopathic membranous nephropathy.

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection in idiopathic membranous nephropathy (IMN) patients, who are treated with immunosuppressive drugs. However, the risk factors of infection and their prognosis are rarely investigated. We aimed to characterize the clinical manifestations of PCP in patients with IMN, and to understand their risk factors, so that we can provide early warnings to patients with high risk and potential poor prognosis. We conducted a retrospective observational study of IMN patients in a referral center in China, from Jan 2012 to Dec 2018. Clinical and laboratory data were collected separately at the time of IMN and PCP diagnosis. Patients with PCP were matched to those without by gender and age at a ratio of 1:4. The risk factors and prognostic factors were determined by univariate and multivariate logistic regression analysis. A total of 879 patients with IMN were included, with a median follow-up of 267 (interquartile range (IQR) 64,842) days. In total, 26 (2.96%) of them were diagnosed with PCP. The infection rate increased to 3.87% among patients who received corticosteroids, and it further increased to 5.49% in those received over 0.5mg/kg prednisone. Univariate analysis indicated that initial usage of corticosteroids, use of cyclophosphamide, reduced estimated glomerular filtration rate (eGFR), and higher 24-h proteinuria were related to the PCP susceptibility. Multivariate analysis revealed that corticosteroid treatment and reduced eGFR increased the risk of the Pneumocystis jirovecii infection. The case fatality rate of the PCP patients was 23.08%, and increased to 75% among patients requiring invasive ventilation. Univariate analysis indicated that pulmonary insufficiency, invasive ventilation, decreased eGFR, and increased lactate dehydrogenase at presentation were linked to poor prognosis. PCP is not rare in patients with IMN, especially those on corticosteroids, and presented with decreased eGFR. Considering the high case fatality rate, further studies are in need for prevention and management of these patients.

Preadmission Corticosteroid Therapy and the Risk of Respiratory Failure in Adults Without HIV Presenting With Pneumocystis Pneumonia.

BACKGROUND: Corticosteroid therapy is a well-recognized risk factor for Pneumocystis pneumonia (PCP); however, it has also been proposed as an adjunct to decrease inflammation and respiratory failure. OBJECTIVE: To determine the association between preadmission corticosteroid use and risk of moderate-to-severe respiratory failure at the time of PCP presentation. METHODS: This retrospective cohort study evaluated HIV-negative immunosuppressed adults diagnosed with PCP at Mayo Clinic from 2006 to 2016. Multivariable regression models were used to evaluate the association between preadmission corticosteroid exposure and moderate-to-severe respiratory failure at presentation. RESULTS: Of the 323 patients included, 174 (54%) used preadmission corticosteroids with a median daily dosage of 20 (interquartile range: 10-40) mg of prednisone or equivalent. After adjustment for baseline demographics, preadmission corticosteroid therapy did not decrease respiratory failure at the time of PCP presentation (odds ratio: 1.23, 95% confidence interval: 0.73-2.09, P = .38). Additionally, after adjusting for inpatient corticosteroid administration, preadmission corticosteroid use did not impact the need for intensive care unit admission (P = .98), mechanical ventilation (P = .92), or 30-day mortality (P = .11). CONCLUSIONS: Corticosteroid exposure before PCP presentation in immunosuppressed HIV-negative adults was not associated with a reduced risk of moderate-to-severe respiratory failure.

Hypercalcemia Heralding Pneumocystis jirovecii Pneumonia in an HIV-Seronegative Patient with Diffuse Cutaneous Systemic Sclerosis.

Pneumocystis pneumonia (PCP) is a life-threatening fungal infection occurring in immunocompromised patients such as HIV-positive patients with low CD4 cell count or patients under heavy immunosuppressive therapy. We report the case of a 59-year-old male with severe diffuse cutaneous systemic sclerosis presenting with asthenia, dry cough and worsening shortness of breath for the last 15 days. Biological studies were remarkable for PTH-independent severe hypercalcemia with low 25-hydroxyvitamin D and a paradoxically elevated 1,25-dihydroxyvitamin D. Early bronchoalveolar lavage allowed for PCP diagnosis and targeted treatment. We discuss the underlying physiopathology and difficulties regarding prophylaxis and treatment.

Characteristics of pulmonary complications in non-Hodgkin's lymphoma patients treated with rituximab-containing chemotherapy and impact on survival.

Patients with non-Hodgkin's lymphoma (NHL) receiving rituximab-containing chemotherapy are at risk of developing respiratory complications, but comprehensive information on these complications and their impact on survival is lacking. We performed a retrospective cohort analysis on 123 NHL patients who received rituximab-containing chemotherapy between 2009 and 2016 in order to describe the incidence, etiologies and effect on survival of respiratory complications defined by new or worsening respiratory symptoms requiring diagnostic work-up or hospitalization. Thirty patients (24%) developed respiratory complications during a follow-up time of 825 (555-1338) days after chemotherapy. They had a higher prevalence of congestive heart failure and lung or pleural involvement at diagnosis as compared to patients who did not develop complications. Overall, 58 episodes of pulmonary complications were observed after median (interquartile) times from the first and last rituximab doses of 205 (75-580) days and 27 (14-163) days respectively. Infectious etiologies accounted for 75% of the respiratory complications, followed by heart failure exacerbation, lymphomatous involvement, and ARDS. Two Pneumocystis jirovecii pneumonias were observed, and no complication was ascribed to rituximab toxicity. Respiratory complications required ICU admission in 19 cases (33%) and invasive mechanical ventilation in 14 cases (24%). Using a time-dependent Cox regression analysis, we observed that the occurrence of respiratory complications was associated with a 170% increase in death hazard (hazard ratio 2.65, 95% CI 1.60-4.40, p = 0.001). In conclusion, respiratory complications in NHL patients receiving chemotherapy are relatively frequent, severe, and mostly infectious and are associated with increased mortality.

[Clinical Features of Pneumocystis Jiroveci Pneumonia in Patients with Inflammatory Bowel Disease].

Objective To investigate the clinical features of patients with inflammatory bowel disease (IBD) complicated with Pneumocystis Jiroveci Pneumonia (PJP). Methods We retrospectively analyzed the clinical data of 5 patients who were hospitalized in Peking Union Medical College Hospital from January 2012 to July 2017 for treatment of IBD complicated with PJP. Demographic characteristics,clinical manifestations,treatments,and outcomes were descriptively analyzed. Results Of these five patients,four had ulcerative colitis (UC) and one had Crohn's disease (CD). All patients were males,with an average age of (61.8±1.9) years. All patients were in active disease status and had symptoms including cough and suffocation. Three patients had hypoxemia,among whom two developed type 1 respiratory failure. Three patients were treated with immunosuppressive medications (corticosteroids and/or immunosuppressant drugs) before the diagnosis of PJP. Lymphocyte counts in three patients were less than 0.6×109/L. CD4+T cells in two patients were less than 200×106/L. Four patients had elevated serum cytomegalovirus DNA. The level of ß-D-glucan was elevated in four patients. Chest CT showed bilateral diffuse ground glass opacification. PJP-DNA was positive in sputum or bronchoalveolar lavage fluid in all patients. Two patients with type 1 respiratory failure required invasive mechanical ventilation. All patients received trimethoprim-sulfamethoxazole and methylprednisolone treatment. Four patients recovered completely and one died. Conclusion Elderly (aged>55 years) IBD patients who are receiving immune-suppressive therapy or with decreased peripheral blood lymphocyte count are at higher risk of PJP.

Type 1 interferons suppress accelerated osteoclastogenesis and prevent loss of bone mass during systemic inflammatory responses to Pneumocystis lung infection.

HIV infection causes loss of CD4(+) T cells and type 1 interferon (IFN)-producing and IFN-responsive dendritic cells, resulting in immunodeficiencies and susceptibility to opportunistic infections, such as Pneumocystis. Osteoporosis and bone marrow failure are additional unexplained complications in HIV-positive patients and patients with AIDS, respectively. We recently demonstrated that mice that lack lymphocytes and IFN a/b receptor (IFrag(-/-)) develop bone marrow failure after Pneumocystis lung infection, whereas lymphocyte-deficient, IFN α/ß receptor-competent mice (RAG(-/-)) had normal hematopoiesis. Interestingly, infected IFrag(-/-) mice also exhibited bone fragility, suggesting loss of bone mass. We quantified bone changes and evaluated the potential connection between progressing bone fragility and bone marrow failure after Pneumocystis lung infection in IFrag(-/-) mice. We found that Pneumocystis infection accelerated osteoclastogenesis as bone marrow failure progressed. This finding was consistent with induction of osteoclastogenic factors, including receptor-activated nuclear factor-κB ligand and the proapoptotic factor tumor necrosis factor-related apoptosis-inducing ligand, in conjunction with their shared decoy receptor osteoprotegerin, in the bone marrow of infected IFrag(-/-) mice. Deregulation of this axis has also been observed in HIV-positive individuals. Biphosphonate treatment of IFrag(-/-) mice prevented bone loss and protected loss of hematopoietic precursor cells that maintained activity in vitro but did not prevent loss of mature neutrophils. Together, these data show that bone loss and bone marrow failure are partially linked, which suggests that the deregulation of the receptor-activated nuclear factor-κB ligand/osteoprotegerin/tumor necrosis factor-related apoptosis-inducing ligand axis may connect the two phenotypes in our model.

Prevention of bone marrow cell apoptosis and regulation of hematopoiesis by type I IFNs during systemic responses to pneumocystis lung infection.

We recently demonstrated that lack of type I IFN signaling (IFNAR knockout) in lymphocyte-deficient mice (IFrag(-/-)) results in bone marrow (BM) failure after Pneumocystis lung infection, whereas lymphocyte-deficient mice with intact IFNAR (RAG(-/-)) had normal hematopoiesis. In the current work, we performed studies to define further the mechanisms involved in the induction of BM failure in this system. BM chimera experiments revealed that IFNAR expression was required on BM-derived but not stroma-derived cells to prevent BM failure. Signals elicited after day 7 postinfection appeared critical in determining BM cell fate. We observed caspase-8- and caspase-9-mediated apoptotic cell death, beginning with neutrophils. Death of myeloid precursors was associated with secondary oxidative stress, and decreasing colony-forming activity in BM cell cultures. Treatment with N-acetylcysteine could slow the progression of, but not prevent, BM failure. Type I IFN signaling has previously been shown to expand the neutrophil life span and regulate the expression of some antiapoptotic factors. Quantitative RT-PCR demonstrated reduced mRNA abundance for the antiapoptotic factors BCL-2, IAP2, MCL-1, and others in BM cells from IFrag(-/-) compared with that in BM cells from RAG(-/-) mice at day 7. mRNA and protein for the proapoptotic cytokine TNF-α was increased, whereas mRNA for the growth factors G-CSF and GM-CSF was reduced. In vivo anti-TNF-α treatment improved precursor cell survival and activity in culture. Thus, we propose that lack of type I IFN signaling results in decreased resistance to inflammation-induced proapoptotic stressors and impaired replenishment by precursors after systemic responses to Pneumocystis lung infection. Our finding may have implications in understanding mechanisms underlying regenerative BM depression/failure during complex immune deficiencies such as AIDS.

Chitinases in Pneumocystis carinii pneumonia.

Pneumocystis pneumonia remains an important complication of immune suppression. The cell wall of Pneumocystis has been demonstrated to potently stimulate host inflammatory responses, with most studies focusing on ß-glucan components of the Pneumocystis cell wall. In the current study, we have elaborated the potential role of chitins and chitinases in Pneumocystis pneumonia. We demonstrated differential host mammalian chitinase expression during Pneumocystis pneumonia. We further characterized a chitin synthase gene in Pneumocystis carinii termed Pcchs5, a gene with considerable homolog to the fungal chitin biosynthesis protein Chs5. We also observed the impact of chitinase digestion on Pneumocystis-induced host inflammatory responses by measuring TNFα release and mammalian chitinase expression by cultured lung epithelial and macrophage cells stimulated with Pneumocystis cell wall isolates in the presence and absence of exogenous chitinase digestion. These findings provide evidence supporting a chitin biosynthetic pathway in Pneumocystis organisms and that chitinases modulate inflammatory responses in lung cells. We further demonstrate lung expression of chitinase molecules during Pneumocystis pneumonia.

Pneumocystis pneumonia in hospitalized patients: a detailed examination of symptoms, management, and outcomes in human immunodeficiency virus (HIV)-infected and HIV-uninfected persons.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is a life-threatening infection for immunocompromised individuals. Robust data and clear guidelines are available for prophylaxis and treatment of human immunodeficiency virus (HIV)-related PCP (HIV-PCP), yet few data and no guidelines are available for non-HIV-related PCP (NH-PCP). We postulated that prevention and inpatient management of HIV-PCP differed from NH-PCP. METHODS: We performed a retrospective case review of all pathologically confirmed cases of PCP seen at the University of Alabama Medical Center from 1996 to 2008. Data on clinical presentation, hospital course, and outcome were collected using a standardized data collection instrument. Bivariate analysis compared prophylaxis, adjunctive corticosteroids, and clinical outcomes between patients with HIV-PCP and NH-PCP. RESULTS: Our analysis of the cohort included 97 cases of PCP; 65 HIV and 32 non-HIV cases. Non-HIV cases rarely received primary prophylaxis (4% vs. 38%, P = 0.01) and received appropriate antibiotics later in the course of hospitalization (5.2 days vs. 1.1 days, P < 0.005). Among transplant patients, NH-PCP was diagnosed a mean of 1066 days after transplantation and most patients were on low-dose corticosteroids (87%) at the time of disease onset. No significant differences in adjunctive corticosteroid use (69% vs. 77%, P = 0.39) and 90-day mortality (41% vs. 28%, P = 0.20) were detected. CONCLUSIONS: Patients who have undergone organ or stem cell transplant remain at risk for PCP for many years after transplantation. In our cohort, patients who developed NH-PCP were rarely given prophylaxis, and initiation of appropriate antibiotics was significantly delayed compared to cases of HIV-PCP. Medical providers should be aware of the ongoing risk for NH-PCP, even late after transplantation, and consider more aggressive approaches to both prophylaxis and earlier empirical therapy for PCP.

A randomized trial of noninvasive positive end expiratory pressure in patients with acquired immune deficiency syndrome and hypoxemic respiratory failure.

BACKGROUND: Acquired immunodeficiency syndrome (AIDS) is a pandemic disease commonly associated with respiratory infections, hypoxemia, and death. Noninvasive PEEP has been shown to improve hypoxemia. In this study, we evaluated the physiologic effects of different levels of noninvasive PEEP in hypoxemic AIDS patients. METHODS: Thirty AIDS patients with acute hypoxemic respiratory failure received a randomized sequence of noninvasive PEEP (5, 10, or 15 cm H(2)O) for 20 min. PEEP was provided through a facial mask with pressure-support ventilation (PSV) of 5 cm H(2)O and an F(IO(2)) of 1. Patients were allowed to breathe spontaneously for a 20-min washout period in between each PEEP trial. Arterial blood gases and clinical variables were recorded after each PEEP treatment. RESULTS: The results indicate that oxygenation improves linearly with increasing levels of PEEP. However, oxygenation levels were similar regardless of the first PEEP level administered (5, 10, or 15 cm H(2)O), and only the subgroup that received an initial treatment of the lowest level of PEEP (ie, 5 cm H(2)O) showed further improvements in oxygenation when higher PEEP levels were subsequently applied. The P(aCO(2)) also increased in response to PEEP elevation, especially with the highest level of PEEP (ie, 15 cm H(2)O). PSV of 5 cm H(2)O use was associated with significant and consistent improvements in the subjective sensations of dyspnea and respiratory rate reported by patients treated with any level of PEEP (from 0 to 15 cm H(2)O). CONCLUSIONS: AIDS patients with hypoxemic respiratory failure improve oxygenation in response to a progressive sequential elevation of PEEP (up to 15 cm H(2)O). However, corresponding elevations in P(aCO(2)) limit the recommended level of PEEP to 10 cm H(2)O. At a level of 5 cm H(2)O, PSV promotes an improvement in the subjective sensation of dyspnea regardless of the PEEP level employed.

[Pneumocystic pneumonia].

The article is devoted to short description of epidemiology, clinical and radiologic demonstration of pneumocystic pneumonia. The features of pathologicoanatomic changes at pneumocystic pneumonia are described. Own observation about combination of classic and scarce histological changes at this disease is in the article.

[A case of Pneumocystis jirovecii pneumonia after kidney transplantation with re-exacerbation following therapy].

A 55-year-old man who had a living kidney transplant 3 months previously was admitted complaining of 4 days of non-productive cough and fever. Because of his low oxygen saturation (SpO2 83% on room air), ground-glass opacities in both lung fields, and marked elevation of beta-D-glucan, a diagnosis of Pneumocystis jirovecii pneumonia (PCP) was considered. The diagnosis of PCP was confirmed by bronchoalveolar lavage. Subsequently, his oxygenation level decreased even after the administration of trimethoprim-sulfamethoxazole, therefore we concurrently administered 60 mg of prednisolone. His clinical symptoms and radiographic findings gradually improved. However, his respiratory condition and radiographic findings exacerbated again after the tapering of prednisolone. His condition improved after the prednisolone dose was returned to 30 mg per day. This case suggested that, in the treatment of PCP in patients without human immunodeficiency virus (HIV) infection, reduction of steroids may cause exacerbation of PCP, similar to immune reconstitution inflammatory syndrome which occurs in HIV patients.

[Current course of pneumocystic pneumonia in HIV-infected patients].

AIM: To describe clinical and laboratory characteristics of pneumocystic pneumonia (PP) in patients with HIV-infection for improvement of diagnosis quality. MATERIAL AND METHODS: Detailed examination was performed in 111 HIV-infected patients with suggested diagnosis of PP. The following investigations were made: clinical, x-ray examinations, total count and biochemical blood tests, enzyme immunoassay, indirect immunofluorescence reaction (II-FR) for Pneumocystis jiroveci antigens in bronchoalveolar lavage fluid (BALF) or induced sputum. For diagnosis of other secondary diseases PCR was used for investigation of BALF and bronchial biopsy to detect DNA of Mycobacterium tuberculosis complex, Candida albicans, Cytomegalovirus, Toxoplasma gondii, Mycoplasma spa., Herpes simplex I, II. DNA of cytomegalovirus in blood was detected with PCR. Microscopic tests of the sputum were conducted for detection of acid-resistant mycobacteria. RESULTS: PP was associated with other secondary diseases in 59% patients (pulmonary tuberculosis ---16%, CMV pneumonia--31%, combination of all the lesions--5%). PP diagnosis was cancelled and pulmonary tuberculosis was diagnosed in 12 patients. In combination of PP with other pathology dominant were symptoms observed in PP monoinfection and only effective anti-pneumocystic treatment revealed signs of comorbid pathology. Tuberculosis patients had weaker signs of respiratory failure, symmetric bilateral interstitial or small-focal alterations were detected less frequently. CONCLUSION: Current PP course characteristics in HIV infection are identified. In clinical diagnosis of PP special attention should be paid to data complex especially to increasing respiratory failure, high ESR, elevated lactate dehydrogenase, low blood pO2, fast response to ex juvantibus therapy. The most effective method of the diagnosis verification--BALF IIFR.

Clinical characteristics and prognosis of patients with Pneumocystis jirovecii pneumonia without a compromised illness.

OBJECTIVE: Pneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP development in patients who were not immunocompromised, but the clinical course and prognosis of PCP are not well understood. We compared the clinical characteristics and prognoses between patients with and without immunocompromised conditions who developed PCP. METHODS: We retrospectively analyzed patients who had been treated for PCP from three hospitals. We defined immunocompromised (IC) status as following: human immunodeficiency virus (HIV) infection; hematological malignancy; solid organ tumor under chemotherapy; rheumatic disease; medication with immunosuppressive agents. Patients without immunocompromised status were defined as being non-immunocompromised (non-IC). RESULTS: The IC and non-IC groups comprised 173 and 14 patients. The median ages were 62.0 and 74.0 years in the IC and the non-IC group, respectively. The median interval between admission and anti-PCP treatment was significantly longer for patients in the non-IC group than that for patients in the IC group (7 vs. 2 days). The in-hospital mortality rates were significantly higher for patients in the non-IC group than that for patients in the IC group (71.4% vs. 43.9%; P = 0.047). A longer interval between admission and anti-PCP therapy was associated with increased 90-day mortality rate in patients with PCP (hazard ratio, 1.082; 95% confidence interval, 1.015-1.153; P = 0.016). CONCLUSIONS: Patients with PCP with no predisposing illnesses were older and had higher mortality rates than IC patients with PCP. Delayed anti-PCP treatment was associated with increased 90-day mortality.

Pneumocystis jiroveci pneumonia with cytomegalovirus infection diagnosed by metagenomic next-generation sequencing in a patient with nephrotic syndrome: A case report.

INTRODUCTION: Opportunistic infection with multiple pathogens currently has become less uncommon since the application of immunosuppressant or corticosteroid in non- Human immunodeficiency virus patients. However, the clinical diagnosis of the co-infection remains difficult since the uncertainty and deficiency of the microbiologic testing methods. PATIENT CONCERNS: A 66-year-old male patient was admitted to our hospital with chest stuffiness, shortness of breath and elevated body temperature. DIAGNOSIS: He was diagnosed with the co-infection of Pneumocystis jiroveci and cytomegalovirus by metagenomic next-generation sequencing of bronchoalveolar lavage fluid after bronchoscopy. INTERVENTIONS: The patient was empirically treated with broad-spectrum antibiotics, trimethoprim/ sulfamethoxazole and ganciclovir in the beginning of the admission. OUTCOMES: The condition of this patient was not improved even with the intervention at the early stage of the disease. His family requested discharge after 24 inpatient days. LESSONS: This case highlights the application of metagenomic next-generation sequencing in the clinical diagnosis of pulmonary co-infection. Suitable prophylaxis, necessary clinical awareness and accurate diagnosis are indispensable for immunocompromised patients with pulmonary infection.

Role of microorganisms in interstitial lung disease.

PURPOSE OF REVIEW: To review the role of microorganisms in interstitial lung disease (ILD) and to emphasize their importance in initiation and course of ILD. RECENT FINDINGS: ILD can be idiopathic but often causality such as drugs or connective tissue disease can be found. Multiple microorganisms have been associated with ILD. On the one hand, pulmonary infection can cause extensive pulmonary damage with patterns of an ILD. On the other hand, microorganisms can trigger the immune system and provoke an abnormal response- not directed against the causative pathogen- that may result in ILD. Moreover, patients with ILD often are susceptible to infection, and infections can importantly influence the course of ILD. Furthermore, not only an infection but also its treatment can result in a drug-induced pneumonitis, eventually resulting in long-term lung damage. SUMMARY: Microorganisms can initiate and/or influence the course of ILD. Early recognition, adequate diagnostic evaluation and therapy are essential to prevent permanent damage. Prevention of infection in patients with established ILD is strongly recommended.

Pneumocystis jirovecii and cystic fibrosis.

Pneumocystis jirovecii is an atypical opportunistic fungus with lung tropism and worldwide distribution that causes pneumonia in immunosuppressed individuals. The development of sensitive molecular techniques has led to the recognition of a colonization or carrier state of P. jirovecii, in which low levels of the organism are detected in persons who do not have pneumonia. Pneumocystis colonization has been described in individuals with various lung diseases, and accumulating evidence suggests that it may be a relevant issue with potential clinical impact. Only a few published studies carried out in Europe have evaluated the prevalence of Pneumocystis colonization in patients with cystic fibrosis, reporting ranges from 1.3-21.6%. The evolution of P. jirovecii colonization in cystic fibrosis patients is largely unknown. In a longitudinal study, none of the colonized patients developed pneumonia during a 1-year follow-up. Since patients with cystic fibrosis could act as major reservoirs and sources of infection for susceptible individuals further research is thus warranted to assess the true scope of the problem and to design rational preventive strategies if necessary. Moreover, it's necessary to elucidate the role of P. jirovecii infection in the natural history of cystic fibrosis in order to improve the clinical management of this disease.

Parenchymal cell TNF receptors contribute to inflammatory cell recruitment and respiratory failure in Pneumocystis carinii-induced pneumonia.

The opportunistic organism Pneumocystis carinii (Pc) produces a life-threatening pneumonia (PcP) in patients with low CD4(+) T cell counts. Animal models of HIV-AIDS-related PcP indicate that development of severe disease is dependent on the presence of CD8(+) T cells and the TNF receptors (TNFR) TNFRsf1a and TNFRsf1b. To distinguish roles of parenchymal and hematopoietic cell TNF signaling in PcP-related lung injury, murine bone marrow transplant chimeras of wild-type, C57BL6/J, and TNFRsf1a/1b double-null origin were generated, CD4(+) T cell depleted, and inoculated with Pc. As expected, C57 --> C57 chimeras (donor marrow --> recipient) developed significant disease as assessed by weight loss, impaired pulmonary function (lung resistance and dynamic lung compliance), and inflammatory cell infiltration. In contrast, TNFRsf1a/1b(-/-) --> TNFRsf1a/1b(-/-) mice were relatively mildly affected despite carrying the greatest organism burden. Mice solely lacking parenchymal TNFRs (C57 --> TNFRsf1a/1b(-/-)) had milder disease than did C57 --> C57 mice. Both groups of mice with TNFR-deficient parenchymal cells had low bronchoalveolar lavage fluid total cell counts and fewer lavageable CD8(+) T cells than did C57 --> C57 mice, suggesting that parenchymal TNFR signaling contributes to PcP-related immunopathology through the recruitment of damaging immune cells. Interestingly, mice with wild-type parenchymal cells but TNFRsf1a/1b(-/-) hematopoietic cells (TNFRsf1a/1b(-/-) --> C57) displayed exacerbated disease characterized by increased MCP-1 and KC production in the lung and increased macrophage and lymphocyte numbers in the lavage, indicating a dysregulated immune response. This study supports a key role of parenchymal cell TNFRs in lung injury induced by Pc and a potential protective effect of receptors on radiosensitive, bone marrow-derived cells.

Dyspnea in homosexual male patients: throwback to an occasionally forgotten but severe clinical presentation of HIV/AIDS.

Pneumocystis jirovecii pneumonia (PJP) can be a severe indicator disease of acquired immunodeficiency syndrome (AIDS). We present two cases of homosexual male patients who came to the emergency unit of a Belgian hospital because of shortness of breath. Both men had been sent back home, initially diagnosed with a benign viral infection. Because of worsening symptoms and gradually evolving hypoxemia, both patients came back and were admitted to the hospital with a diagnosis of (microbiology proven) Pneumocystis jirovecii pneumonia. HIV serology in both men was tested and was clearly positive, indicating a new diagnosis of HIV infection. In this article, we provide an overview of this possibly severe AIDS defining condition. First, we give an introduction of the history of HIV/AIDS and its occurrence in homosexual males in Europe. Secondly, we provide an overview of the diagnosis and treatment of Pneumocystis jirovecii pneumonia. Finally, since the first case reports of Pneumocystis jirovecii pneumonia at the beginning of the AIDS epidemic also included homosexual men, we emphasize the potential importance of a sexual anamnesis in young male patients with an initial complaint of dyspnea.

Pneumocystis pneumonia, a COVID-19 mimic, reminds us of the importance of HIV testing in COVID-19.

While clinical environments are highly focused on COVID-19, reports of missed or delayed treatment for conditions that imitate COVID-19, such as pneumonia caused by the fungus Pneumocystis jirovecii, are emerging. Given the uncertain spectrum of COVID-19 presentations and variable sensitivity of laboratory tests for SARS-CoV-2, there is a risk that, without a high index of suspicion, alternative aetiologies may be overlooked while pursuing a diagnosis of COVID-19. The British HIV Association has been calling for the inclusion of HIV testing in all patients admitted to hospital with suspected COVID-19. In this article we reflect on the importance of including HIV testing to prevent avoidable morbidity and mortality in our patients.