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Microorganisms, Cytokine Patterns, and Pneumonia
The inflammatory response in community-acquired pneumonia (CAP) depends on the host and on the challenge of the causal microorganism. Here, we analyze the patterns of inflammatory cytokines, procalcitonin (PCT), and C-reactive protein (CRP) in order to determine their diagnostic value.
Methods:This was a prospective study of 658 patients admitted with CAP. PCT and CRP were analyzed by immunoluminometric and immunoturbidimetric assays. Cytokines (tumor necrosis factor-α [TNF-α], IL-1β, IL-6, IL-8, and IL-10) were measured using enzyme immunoassay.
Results:The lowest medians of CRP, PCT, TNF-α, and IL-6 were found in CAP of unknown cause, and the highest were found in patients with positive blood cultures. Different cytokine profiles and biomarkers were found depending on cause: atypical bacteria (lower PCT and IL-6), viruses (lower PCT and higher IL-10), Enterobacteriaceae (higher IL-8), Streptococcus pneumoniae (high PCT), and Legionella pneumophila (higher CRP and TNF-α). PCT ≥ 0.36 mg/dL to predict positive blood cultures showed sensitivity of 85%, specificity of 42%, and negative predictive value (NPV) of 98%, whereas a cutoff of ≤ 0.5 mg/dL to predict viruses or atypicals vs bacteria showed sensitivity of 89%/81%, specificity of 68%/68%, positive predictive value of 12%/22%, and NPV of 99%/97%. In a multivariate Euclidean distance model, the lowest inflammatory expression was found in unknown cause and the highest was found in L pneumophila, S pneumoniae, and Enterobacteriaceae. Atypical bacteria exhibit an inflammatory pattern closer to that of viruses.
Conclusions:Different inflammatory patterns elicited by different microorganisms may provide a useful tool for diagnosis. Recognizing these patterns provides additional information that may facilitate a broader understanding of host inflammatory response to microorganisms.
Immediate Respiratory Effects of e-Cigarette Use
Debate exists over the scientific evidence for claims that electronic cigarettes (e-cigarettes) have no health-related ramifications. This study aimed to assess whether using an e-cigarette for 5 min has an impact on the pulmonary function tests and fraction of exhaled nitric oxide (Feno) of healthy adult smokers.
Methods:Thirty healthy smokers (aged 19-56 years, 14 men) participated in this laboratory-based experimental vs control group study. Ab lib use of an e-cigarette for 5 min with the cartridge included (experimental group, n = 30) or removed from the device (control group, n = 10) was assessed.
Results:Using an e-cigarette for 5 min led to an immediate decrease in Feno within the experimental group by 2.14 ppb (P = .005) but not in the control group (P = .859). Total respiratory impedance at 5 Hz in the experimental group was found to also increase by 0.033 kPa/(L/s) (P < .001), and flow respiratory resistance at 5 Hz, 10 Hz, and 20 Hz also statistically increased. Regression analyses controlling for baseline measurements indicated a statistically significant decrease in Feno and an increase in impedance by 0.04 kPa/(L/s) (P = .003), respiratory resistance at 5 Hz by 0.04 kPa/(L/s) (P = .003), at 10 Hz by 0.034 kPa/(L/s) (P = .008), at 20 Hz by 0.043 kPa/(L/s) (P = .007), and overall peripheral airway resistance (β, 0.042 kPa/[L/s]; P = .024), after using an e-cigarette.
Conclusions:e-Cigarettes assessed in the context of this study were found to have immediate adverse physiologic effects after short-term use that are similar to some of the effects seen with tobacco smoking; however, the long-term health effects of e-cigarette use are unknown but potentially adverse and worthy of further investigation.
Remodeling in Severe Asthma
The clinical manifestations of bronchial remodeling in asthma and the potential impact of this process on lung function remain unclear. We aimed to determine whether the presence of pathologic features of airway remodeling in patients with asthma was associated with steroid responsiveness in the short term.
Methods:Sixty-three consecutive patients with severe asthma with chronic airflow impairment (post-bronchodilator FEV1 < 80% predicted values) were recruited, clinically characterized, and had an initial bronchoscopy where endobronchial biopsy and BAL were performed. BAL cellular content was reported and reticular basement membrane (RBM) thickness was measured by validated repeated measures. Patients were then treated with 1 mg/kg/d of methyl prednisone, directly administered IV, for 10 days. A threshold of 15% FEV1 improvement was used to discriminate responsive (group 1) and refractory patients (group 2).
Results:Thirty-eight patients had a steroid responsiveness > 15% (group 1) and a thinner RBM at the biopsy level (5.78 ± 2.0 μm vs 7.60 ± 2.2 μm; P = .001) compared with nonsteroid responsive group 2 patients as defined. The best predictors for being unresponsive were no long-term treatment with oral steroids and increased RBM thickness. The associated receiver operating characteristic curve indicated that RBM thickness could predict steroid responsiveness below 15% with an area under the curve of 0.747 (P = .0002) at a threshold of 7 μm.
Conclusions:Features of airway remodeling are associated with limited short-term steroid responsiveness in severe asthma.
Genetics and Toxins in Pulmonary Hypertension
Pulmonary arterial hypertension (PAH) is a rare complication of hereditary hemorrhagic telangiectasia (HHT). The triggers that promote the development of PAH in HHT remain poorly understood.
We present the case of a 45-year-old woman with decompensated right-sided heart failure secondary to newly diagnosed PAH. The clinical diagnosis of HHT was confirmed on the basis of recurrent spontaneous epistaxis, multiple typical mucocutaneous telangiectasia, and the presence of pulmonary arteriovenous malformation. There was also a suggestive family history. The patient was discovered to have active and extensive stimulant abuse in addition to HHT.
We concluded that there may be a temporal relationship between exposure to stimulants and development of PAH in a host with underlying gene mutation. This case highlights the paradigm of PAH development after environmental exposure in a genetically susceptible host.