Localized amyloidomas are characterized by a benign course and are not associated with systemic amyloidosis. Despite its localized nature, tracheobronchial amyloid deposition may be asymptomatic or may result in significant morbidity due to obstructive phenomena. Pulmonary amyloidosis associated with primary systemic amyloidosis generally presents as a diffuse interstitial pattern with or without pleural effusion. Complete survival data indicate that long-term outcome is poor after diagnosis. We describe the largest series of patients diagnosed by bronchoscopic lung biopsy. Despite reports to the contrary, we have found bronchoscopic lung biopsy to be a safe and effective diagnostic technique.
In this exploratory study in patients with clinically progressive IPF, etanercept was well tolerated. Although there were no differences in the predefined endpoints, a decreased rate of disease progression was observed on several measures. Further evaluation of TNF antagonists in the treatment of IPF may be warranted. Clinical trial registered with www.clinicaltrials.gov (NCT 00063869).
Usual interstitial pneumonia (UIP) is a specific histological pattern of interstitial pneumonia most often associated with the clinical syndrome of idiopathic pulmonary fibrosis (IPF). There is controversy regarding the use of surgical lung biopsy in the diagnosis of UIP, and the risk of lung biopsy in these patients is largely unknown. This study investigated the 30 day surgical mortality rate in patients undergoing surgical lung biopsy for UIP.Patients undergoing surgical lung biopsy over a 10-yr period from 1986–1995 with the ultimate diagnosis of UIP (with or without underlying connective tissue disease) were identified. Pathology, computed tomography, medical records, and survival were assessed.Ten of sixty patients with usual interstitial pneumonia were found to be dead within 30 days of surgical biopsy. All of these were patients with idiopathic UIP, unassociated with connective tissue disease (clinical condition of IPF).In conclusion, patients with usual interstitial pneumonia of the idiopathic type, who present with atypical features, may be at higher risk for death following surgical biopsy than patients presenting with more typical features or patients with other interstitial illnesses.
SARS-CoV-2 mRNA vaccination induces robust humoral and cellular immunity in the circulation; however, it is currently unknown whether it elicits effective immune responses in the respiratory tract, particularly against variants of concern (VOCs), including Omicron. We compared the SARS-CoV-2 S–specific total and neutralizing antibody responses, and B and T cell immunity, in the bronchoalveolar lavage fluid (BAL) and blood of COVID-19–vaccinated individuals and hospitalized patients. Vaccinated individuals had significantly lower levels of neutralizing antibody against D614G, Delta (B.1.617.2), and Omicron BA.1.1 in the BAL compared with COVID-19 convalescents despite robust S-specific antibody responses in the blood. Furthermore, mRNA vaccination induced circulating S-specific B and T cell immunity, but in contrast to COVID-19 convalescents, these responses were absent in the BAL of vaccinated individuals. Using a mouse immunization model, we demonstrated that systemic mRNA vaccination alone induced weak respiratory mucosal neutralizing antibody responses, especially against SARS-CoV-2 Omicron BA.1.1 in mice; however, a combination of systemic mRNA vaccination plus mucosal adenovirus-S immunization induced strong neutralizing antibody responses not only against the ancestral virus but also the Omicron BA.1.1 variant. Together, our study supports the contention that the current COVID-19 vaccines are highly effective against severe disease development, likely through recruiting circulating B and T cell responses during reinfection, but offer limited protection against breakthrough infection, especially by the Omicron sublineage. Hence, mucosal booster vaccination is needed to establish robust sterilizing immunity in the respiratory tract against SARS-CoV-2, including infection by the Omicron sublineage and future VOCs.
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